Therapeutics FINAL EXAM

Weak evidence risk factors for delirium

#1 - *BENZOS - lorazepam and midazolam* hence another reason we try to avoid versed in the ICU -Gender -Anticholinergics -Steroids (really unclear evidence)

MTX adverse effects to consider

#1 monitor for *hematologic toxicity (leukopenia and thrombocytopenia)* You are preventing growth of rapidly dividing cells: *GI and mucosal toxicity* - N/V/D and stomatitis *Dermatologic effects*: Dermatitis, rash, alopecia, photosensitivity Rare *SJS risk* *Hepatotoxicity concern* -Transaminitis is possible but is generally mild and self-limiting and is *dose-related* -Rarely fatty liver disease and hepatic fibrosis, but possible with chronic use -Consider *PREDISPOSING factors - obesity, alcohol use disorder or DM*

HBeAb or anti-HBeAg

(+) = CHRONIC infection (like your IgG) -Means infection is *"resolved"*. -Long term HBV clearance (during treatment) = spontaneous conveersion from *HBe antigen to HBe antibody SEROCONVERSION*

IgM anti-HBc

(+) = acute infection -Present in recent *ACUTE ONLY* HBV infection (< 6 months)

HBcAg

(+) = infectious -Nucleocapsid protein -Expression promotes immune-mediated cell death - lymphocytes attack -Indicates *active HBV replication* (like HBeAg) *Indicates ACTIVE HBV replication*

HBeAg

(+) = infectious -Secreted product of HBV nucleocapsid gene -Present during *ACTIVE HBV replication in acute HBV* -Replaced by anti-HBeAG or HBeAb once infection is resolved - *SEROCONVERSION* -HBeAg-negative mutants = refractory to treatment *MONITOR RESPONSE TO TREATMENT*

HBsAg

(+) = infectious. Used to *DIAGNOSE ACTIVE HBV* (acute or chronic) -Surface protein detectable at *onset* of clinical symptoms - *acute infection* -Detectable *> 6 months indicates chronic infection* -Body produces Abs to HBsAg and this antigen is used for the HBV vaccine *Clearance = favorable outcomes*

Lab abnormalities in RA

(+) Rheumatoid factor (+) Anticyclic *citrullinated peptic (anti-CCP) antibodies* Increased *erythrocyte sedimentation* rate (0-20 normal) Increased *CRP* May have elevated WBCs without infection

MAP Equation

(SBP + 2DBP)/3

Therapies for HBV infection

*"Old"* -Interferon alfa-2b or pegylated interferon alfa-2a *Nucleoside/tide Analogues* -Adefovir dipivoxil -Lamivudine -Entecavir -Telbivudine -Tenofovir

Recommended vasoactive agents for septic shock (vasopressors)

*#1 = Norepi* Epinephrine if needed in ADDITION to NE or Vasopressin in addition to NE at *set 0.03 U/min rate* Dopamine can be used in select patients instead of NE - must be at low risk of tachyarrhythmia

Lipid caloric contribution in TPN (KNOW)

*10 kcal/g* *Caloric content depends on product used* 10% = 1.1. kcal/mL 20% = 2 kcal/mL 30% = 3 kcal/mL

3 in 1 versus 2 in 1 PN Admixture

*3 in 1* -Includes ALL components including IVFE in one container *2 in 1* -IVFE is infused separately through Y site or separate IV cath or lumen ALWAYS check IV compatibilities

Mavyret (glecaprevir/pibrentasvir) dosing

*3* FDC tablets once daily Covers all genotypes

Dextrose caloric yield in TPNs

*3.4 kcal/g* Will provide the most calories of anything in TPN and is the *primary energy source* Dex is used for cell metabolism, body protein preservation, tissue formation, and cellular growth

Caloric contribution of protein

*4 calories per gram (kcal/g)*

Duration of therapy for PPI with NSAID induced PUD

*4 weeks* Can extend to *12 weeks* if the NSAID (includes aspirin) is to be continued Eradicate H. pylori first if present -Educate patients on risk and complications, importance of adherence, etc.

MTX Pk and DDI considerations

*80% excreted unchanged in urine* - consider dose reducing if *CrCl < 60 mL/min* Also 50% plasma protein bound - consider hypoalbuminemia *DDIs: NOT really relevant at low doses for RA* -NSAIDs decrease GFR and compete for active tubular secretion -PCN competes -PPIs can INCREASE oral absorption and reduce elimination

Acute malnuitrition

*< 3 months* Protein depletion with *adequate fat stores* Can result from major infection, surgery, burns, trauma, etc.

Chronic malnutrition

*> 3 months* Protein AND fat depletion Long history of poor nutritional intake Organ failure, pancreatic cancer, RA, IBD, CF, chronic lung disease

ACS and NCI mammogram recommendations

*ACS* -Mammogram annually if *> 40 yo* -ACS always is the safest *NCI* -Mammogram anually if *> 50 yo*

Adverse effects and considerations with misoprostol

*ADEs are major limitation* -DIARRHEA in 10-30% -Abdominal pain -HA -N//V -Flatulence -Hypophosphatemia *Pregnancy CAT X* Monitoring: -Pregnancy test -Serum *phosphate*

ATG vs Basiliximab Comparison

*ATG* -Polyclonal -T-cell DEPLETING -Need pre-medication (cytokine depleting) -Increased infection risk -BOTH induction AND treat rejection *Basiliximab* -Monclonal -T-cell NON-depleting -No need for pre-medication -Well-tolerated -INDUCTION ONLY

ATG vs. Basiliximab

*ATG* -T-cell DEPLETING -Need to premed to prevent CRS -Increased risk of infection -Both *induction AND rejection treatment* *Basiliximab* -T-cell NON-depleting -No need for premedication -Well tolerated, RARE hypersensitivity -*ONLY for induction* -*No real infection risk*

Adefovir Dipivoxil for HBV

*AVOID in HIV unless also receiving a full HAART therapy* *Advantages* -Active in WT AND *LAM-resistant* HBV and combined with *LAM or telbivudine in cirrhosis* -Decrease of *HBV DNA and ALT levels* occured in long term therapy -Low resistance within 1 and 5 years vs LAM, but still higher risk in patients with LAM-resistance in adefovir monotherapy vs combination. Moral: COMBINE *Disadvantages* -Can be used in *compensated* cirrhotic patients but NOT preferred and usually combined with LAM therapy -*Nephrotoxicity* reported at *higher doses (30 mg/day)* - careful because 10 mg/day dosing same as placebo. Monitor renal function closely in patients at risk

Acute vs Chronic HBV infection

*Acute* -Fulminant liver failure is RARE -Full recovery is most common *Chronic HBV infection* -Diagnostics: HBsAg (+) fir > 6 months, 2-5x UNL increase in AST/ALTm detectable HBeAg (sometimes negative). Should have seroconverted to Ab if resolved -MUST TREAT HBV chronic infections are NOT curable: the coal is to suppress HBV replication and prevent progression to cirrhosis and HCC*

Side effects of corticosteroids

*Acute* -Headache -Mood disturbance and insomnia -Hypertension -Na and fluid retention -Hypokalemia -Glucose intolerance -Abdominal fat distribution -Impaired wound healing and acne *Chronic Long Term* -Cataracts -Glaucoma -Suppression of growth and menstrual irregularities -Osteoporosis -Loss of muscle mass, muscle weakness, and steroid myopathy

Acute vs Chronic Treatments for IBD

*Acute* -Steroids -Aminosalicylates -Biologics -Antibiotics -Methotrexate -Cyclosporine -Tacro *Chronic ONLY* -Azathioprine -6-MP

Clinical presentation of breast cancer in advanced or metastatic disease

*Advanced* -Prominent skin edema -Redness and warmth -Induration of underlying tissue *Distant or metastatic (think about where it can go)* -Difficulty breathing -Abdominal enlargement -Jaundice -Bone pain -Mental status change *Associated syndromes* -Hypercalcemia -Pain -Brain metastases -Hypercoagulability

Tenofovir for HBV

*Advantages* -Can be used in *compensated AND decompensated cirrhosis* -Better treatment success in *LAM resistance and adefovir treatment failure* but may have *adefovir cross-resistance*

Colloids (albumin) vs Crystalloids (LR and NS)

*Albumin* -Require less volume -Require less time -Enhanced colloid oncotic pressure -Improve contractility and CO *Crystalloids* -Expand extracellular compartment effectively -Less increase in extravascular *pulmonary H2O due to rapid equillibrium* -Improved post-op organ function -Minimize anaphylaxis -Less expensive

Minimum and max concentrations in TPN

*All TPN* -Dextrose 10-35% -Protein 4-7.5% *ONLY 3 in 1* -Minimum lipids of 2% concentration

Diagnosis of HCV

*Anti-HCV (HCV antibody)* -If reactive (+), presume HCV infection and TEST HCV RNA PCR -If nonreactive (-) no further action unless there was *exposure in past 6 months* or clinical evidence of HCV *HCV RNA PCR* -Qualitative tests to detect HCV presence or absence -Quantitative tests to detect HCV levels

Indirect (cellular) effects of CMV infection

*Antigen and cytokine expression of CMV leading to allograft injury and rejection. Chronic:* -Atherosclerosis -Bronchiolitis obliterans -Vanishing bile duct syndrome -EBV associated PTLD -Systemic immune suppression leading to opportunistic infections

Management of aromatase inhibitor adverse effects

*Arthralgia's/myalgias* -SNRIs (duloxetine) -SSRIs -Possibly other pain meds *Hot flashes* -SNRIs (VENLAFAXINE) -SSRIs -Gabapentin -Clonidine -Oxybutynin *Can also first try switching to the other AI - sometimes works!*

Remicade biosimilars made and available or not

*Available* -Inflectra -Renflexis *Not Available* -Ixifi

Dobutamine PD

*B-adrenergic INOTROPE* - not technically a vasopressor Increases HR and contractility significantly Preferred for improvement of *CO and oxygen delivery* NOT agent of choice for septic shock

Etiology of breast cancer

*BRCA1 and BRCA2* -Carriers have 80-90% lifetime risk of breast cancer -Ashkenazi Jews have high frequency of 3 genetic mutations (2 BRCA1 and BRCA2) -Prophylactic mastectomy and possibly bilateral oophorectmy can provide gains in life expectancy but is not 100% preventable *p53* -30-50% of breast cancers have p53 mutations *HER2/neu proto-oncogene (erbB-2)* -25-30% of all breast cances -Amplification/overexpression imparts *POORER prognosis* -Used primarily to select patients for herceptin and lapatanib therapy Lots of other risk factors too

ACS Screening Recommendations for average risk patient for CRC

*Beginning at 50 yo* - one of following: 1. FSIG every 5 years 2. CSPY every 10 years 3. DCBE every 5 years 4. CTC every 5 years or 5. gFOBT annually 6. FIT annually 7. sDNA, interval unknown

Validated Pain Assessment tools

*Behavioral Pain Scale (BPS)* -Score of *5 or higher* = pain (0-12 point) -Higher scores MAY indicate increase in pain intensity - validated *Critical Care Pain Observation Tool (CPOT)* -Includes muscle tension and vocalization in assessment -Score of *3 or higher* indicates pain -Higher scores DO NOT necessarily note increased pain

Intestinal complications with UC or CD

*Both* -Fissures or fistulas -Linear clefts -Strictures -Intestinal obstruction -Colorectal cancer *CD* -Skip lesions -Intra-abdominal and perianal abscesses *UC* -Crypt abscesses -*Toxic megacolon if severe enough* (lose contraction of muscle and colon dilates)

Ibrutinib (Imbruvica)

*Bruton tyrosine kinase (BTK) inhibitor* given orally (potent and IRREVERSIBLE) -BTK is an integral component of the *B cell receptor and cytokine receptor paths* -Blocks pathway *upstream of mTOR* Note: *CYP3A4 and 2D6 metabolized* *First line for patients with 17p deletion (no short arm)*

Diagnosis of AML

*CBC with diff* -Anemia, neutropenia, and thrombocytopenia due to crowding out of bone marrow - NONSPECIFIC to AML -Presence of *blasts* on peripheral smear *Histology-Auer rods* *Bone marrow biopsy NEED for definitive Dx* -*> 20% BLASTS* -< 20% blasts if specific recurrent cytogenetic abnormalities (chromosomes 8, 16,17,21) -Immunophenotype/cytogenetics are used to determine patient risk and prognosis

Tysabri (natalizumab) indications

*CD ONLY* - induction and maintenance of response and remission for mod-severe disease failing conventional AND *at least 2 anti-TNF agents* Integrin inhibitor

Cimzia (Certolizumab pegol) indications in IBD

*CD ONLY* - induction in maintenance mod-severe refractory to conventional

Prednisone and hydrocortisone indications

*CD and UC* INDUCTION ONLY - to remission

CAR-T side effects

*CRS main concern* -Flu-like, fever/myalgia if mild *Severe CRS Inlammatory syndrome* -Capillary leak -Pulmonary edema -HYPOTENSION -Coagulopathy (DIC) -Multi system *organ failure* Occurs within *1-14 days after infusion* *NEUROLOGIC Toxicity is big problem and common as well*

Short term impacts of untreated pain

*CV effects* -Tachycardia -HTN -Increased oxygen consumption *Neuroendocrine and metabolic effects* -Increased catecholamines, cortisol, and glucagon -Hyperglycemia -Glucose intolerance and insulin resistance

Cardiogenic shock

*Causes* -Cardiomyopathy -Arrhythmias -MI *Management* -Inotropes (dobutamine) -Revascularization -Remove fluid

Hypovolemic shock

*Causes* -Loss of blood or fluid *Management* -Stop bleeding -IV fluids

Obstructive shock

*Causes* -PE -Cardiac tamponade *Management* -Anticoagulation -Pericardiocentesis for cardiac tamponade

Distributive shock

*Causes* -Sepsis most common -Anaphylactic -Neurogenic *Management* -Fix underlying cause (e.g. treat infection) -IV fluids -Vasopressors

Complications of chronic HBV

*Cirrhosis* -Around 20% of chronic develop. -Risk factors include persistent serum HBV DNA levels, coinfection with HCV, delta hepatitis or HIV, *male, and alcohol use* *Hepatocellular carcinoma (HCC)* -HBV is known risk factor -Can occur without cirrhosis -HBV > HCV -Other risk factors include male, older age, coinfection with HCV, delta hep, cirrhosis, persistent alcohol intake, and persistent serum HBV DNA levels

Super common NSCLC regimen we should know

*Cisplatin AUC6 1 + pemetrexed 500 mg/m2 day 1 every 21 days X 4 CYCLES* Other examples: -Cisplatin day 1 and etoposide days 1-3 Q28 days X 4 cycles -Cisplatin + docetaxel day 1 every 21 days X 4 cycles -Carboplatin AUC6 day 1 and paclitaxel day 1 every 21 days X 4 cycles

Sulfsalazine side effects

*Classic* -Anemia -Hepatotoxicity (rare) *Common* -N/V -HA -Fever -Rash *Fun* -Orange-colored urine and stool *Rare* -Interstitial nephritis -Nephrolithiasis -AKI

Azathioprine and 6-MC side effects

*Classic* -N/V -Malaise -Bone marrow depression (rare) -Pancreatitis -Hepatitis -Allergic reaction *Dose related* -Nausea -Malaise -Infections -Hepatitis -Myelosuppression *Idiosyncratic* -Fever -Rash -Arthralgia -Pancreatitis

Hodgkin lymphoma (10% of lymphomas)

*Classical (95%)* -Lymphocyte depleted -Lymphocyte rich -Mixed cellularity -Nodular sclerosis *Non-classical (5%)*

Dopamine receptor antagonist drugs

*Common and similar* -Prochlorperazine -Promethazine *BOTH QT prolonging* *Different* -Trimethobenzamide - no QT prolongation

H2RA adverse effects and monitoring

*Common* -Headache -Dizziness -Diarrhea -Somnolence -Gynecomastia with cimetidine *Less common* -Thrombocytopenia -Neutropenia -Liver function abnormalities -Renal impairment -Pancreatitis Monitor: -Baseline and periodic CBC -Serum lytes -Renal and liver function

Daunorubicin (and other anthracycline) side effects

*Common* -Myelosuppression -*Mucositis* -N/V -Alopecia *Most concerning* -Cardiac toxicity - arrhythmias and pericarditis with acute tx (AML tx) and chronically CHF and IS related to the CUMULATIVE dose. Obtain a baseline ventricular ejection fraction and repeat every couple cycles to monitor. -Liver dysfunction (*monitor bilirubin*) -Secondary malignancies (*again, major cause of sAML and MDS*)

Hydroxychloroquine adverse effects

*Common* -Nausea and vomiting -Constipation or diarrhea -Rashes -Pruritis -Insomnia -Irritability -*Anxiety* -*Dream disturbance* *Rare, serious* -Retinotoxicity -Cardiotoxicity -Myopathy -Psychosis -Blood dyscrasias

Methotrexate side effects

*Common* -Ulcerative stomatitis -Leukopenia and thrombocytopenia -N/V -Malaise and fatigue -Chills and fever -Dizziness -Susceptibility to infection -Transaminitis (15-50%) *Rare Serious ADEs* -SJS -Interstitial lung disease

Leflunomide (Arava) adverse effects

*Common* -Alopecia -Rash -Dizziness -Headache *Rare* -SJS/TEN -Hepatic injury -Blood dyscrasias -Neuropathy -Interstitial lung disease -*Respiratory infection*

NS5A (-asvir) inhibitor MOA

*Complex replication inhibitors* Functions of NS5A -Essential structure for RNA replication -Binds to cyclophylin A to antagonize and innate immune response -Assembles infectious viral particles *Pan-genotypic activity* but exact mechanisms are unknown. Possibly inhibit hyperphosphorylationq

Persons at "high immunologic risk* in transplant

*Consider ATG induction for all* 1. African American 2. High PRA (plasma renin activity) 3. Donor specific antibody 4. Positive cross-match 5. Previous transplant 6. Pancreas > Kidney > Liver

Options for fluid resucitation

*Crystalloids* -NS -Lactated ringers *Colloid therapies* -Albumin 5% -Hetastarch (NOT used)

Mycophenolate and calcineurin inhibitor DDIs

*Cyclosporine* -Inhibits OATP leading to LOWER levels because mycophenolate is transported by OATP into blood and excretes via kidney *Tacroliimus* -NO significant OATP inhibition and no DDI -May be why tacrolimus had better transplant outcomes

Cyclosporine dose forms

*Cyclosporine* -Oil based or microemulsion formulation -NOT interchangable -ONLY use if patient already on and switching

Osimertinib (Tagrisso) DDIs and adverse effects

*DDIs* -CYP3A4 inducer/inhibitor -PGP -CYP1A2 inducer -BCRP inhibitor *Side effects* -Rash -Diarrhea -Fatigue -Dry skin -*Nail toxicity* -*Eye disorders* -RARE QT prolongation Other TKIs have more side effects - tagrisso is pretty well tolerated

Spontaneous awakening trials (SATs)

*Daily interruption* of sedation to awaken patient to follow 3 or 4 simple commands *Decreases* -Duration of mech vent -ICU LOS -Dx testing for unexplained changes in mental status

Day 1 and *2-4* N/V Prophy with HIGH emetogenic chemo

*Day 1* 1. NK1 antagonist PLUS 5-HT3 antagonist + dexamethasone 2. NK1/5-HT3 antagonist + dexamethasone 3. Olanzapine + 5-HT3 antagonist + dexamethasone *Days 2-4* 1. If aprepitant on day 1, then also on days *2-3* PLUS dexamethasone days 2-4 2. If fosaprepitant or rolapitant on day 1, only dexamethasone days 2-4 (long half life) 3. If olanzapine used day 1, do days 2-4 too

FOLFOX4

*Day 1* 1. Oxaliplatin 85 mg/m2 over 2 hr + LV over 2 hr 2. Follow w/ 5-FU400 mg/m2 IV theen 600 mg/m2 over 22 hours. *Day 2* 1. LV 200 mg/m2 over 2 hours followed by 5-FU 400 mg/m2 IV then 600 mg/m2 over 22 hours Repeat every *2 weeks X 12 weeks*

Day 1 and *2-3* N/V Prophy with MODERATE emetogenic chemo

*Day 1* 1. 5-HT3 antagonist + dexamethasone *+/-* NK1 antagonist 2. NK1/5-HT3 antagonist + dexamethasone 3. Olanzapine + 5-HT3 antagonist + dexamethasone *Days 2-3* 1. If no NK1 on day 1, 5=HT3 antagonist monotherapy days 2-3 OR dexamethasone days 2-3 2. If aprepitant on day 1 then also days 2=3 +/- dexamethasone days 2-3 3. If fosaprepitant, rolapreptiant, or NK1/5HT3 antagonist on day 1 then *+/-* dexamethasone days 2-3* 4. If olanzapine used day 1, also do days 2-3

Hypovolemic shock hemodynamics

*Decreased CO* *Increased SVR* *Decreased preload*

Diagnosis and workup of NH-lymphoma

*Diagnosis* -Needle biopsy -FLOW and/or immunohistochemistry (IHC) - to evaluate cells -Imaging with PET and CT scans to show presence of disease. PET scans absolutely suck you have to drink radioactive nastiness -Gene expression - *MYC, BCL2, and BCL6* *Workup* -CBC -LDH/CMP -HBV/HCV testing -CT chest, abdomen and pelvis -PET (staging) -MUGA/ECHO (to see how the heart is working)

Diet and PUD

*Diet = NOT risk factor* for PUD occurrence and recurrence -Dietary factors can cause *increased dyspepsia* -Includes coffee, tea, carbonated beverages, milk, greasy, and spicy foods. -*Caffeine is a gastric acid stimulant*

Taxane specific drug interaction concerns

*Docetaxel = 3A4 substrate* Paclitaxel = CYP2C8 and *3A4 substrate* - if used with cisplatin, you decrease paclitaxel clearance

Metoclopramide class and action

*Dopamine receptor antagonist AND serotonin antagonist* -Works on the chemoreceptor trigger zone AND in the GIT vomiting center Dosing usually 5-20 mg TID - at lower dose only antagonizes dopamine receptors really

Which type of breast cancer is usually most aggressive

*ER negative* *HER2/neu positive* ER+ tumors are usually less aggressive and slower growing

Basics of breast cancer staging

*Early* -Stages 0, I, and II *Locally advanced or advanced* -Stage III - larger tumor with some extensive nodal involvement *Advanced* -Stage IV -Metastases to organs distant from primary tumor

Indications for nutritional support therapy (starred)

*Enteral Nutrition (EN)* -Patients who are malnourished or under metabolic stress AND -*GIT functional* AND -Protein and energy needs cannot be met via oral route *Parenteral nutrition (PN)* -Patients who are malnourished or under metabolic stress AND -*EN not feasable or CI* DO NOT use NST if patients are well nourished or under little to no metabolic stress

Budensonide formulation indications

*Entocort* -Crohn's ONLY -Induction AND maintenance of remission of mild-moderate active CD involving ileum ileum or ascending colon *Uceris* -Induction and maintenance to remission of mild-moderate disease

Tests that primarily test colorectal cancer

*Fecal occult blood tests (FOBT)* -Guaiac based (gFOOBT) - can decrease mortality by 15-33% -Immunochemical based (FIT) *sDNA*

Fentanyl vs hydromorphone for pain

*Fentanyl* -Faster onset, ofset, and half life shortest -*CYP3A4* metabolism -Can accumulate in obesity due to *lipophilicity* *Dilaudid* -Lower risk compared to morphine of drug accumulation -Only metabolized by glucuronidation in liver

Febrile neutropenia prophylactic drugs

*First do risk stratification* -Antifungals -Antivirals -Antibacterial - levofloxacin -PCP - Bactrim usually or pentamidine, dapsone, atovaquone if CI

Precedex properties

*For 712* -Anxiolytiv -Analgesic -Does NOT depress respiratory drive (can extubate while on) -Great option if patient is going to be extubated in next 48 hours

CMV Treatment Duration per VICTOR/General

*General* -2 weeks PLUS of *BID prophy dosing* -1-3 months of maintenance QD dosing *Victor* -3 weeks induction -4 weeks maintenance

Risk factors for AML

*Genetic disorders* -Down syndrome -Fanconi's anemia (not enough blood cells) -Klinefelters (XXY) -Severe combined immunodeficiency *Drugs* (2 major classes) - this is referred to as treatment related or t-AML and has poor outcomes 1. Alkylating agents (cyclophosphamide, cisplatin, Nitrogen mustards, etc) *5-7 years post-exposure* 2. Topoisomerase II Inhibitors (etoposide, doxorubicin, daunorubicin) - *1-3 years after exposure* *Age* (older=more risk) *Prior Conditions* -Myelodysplastic syndrome (sAML if MDS to AML) *Radiation - big cause* *Chemicals* -Benzene -Ethylene oxide *Viruses*

Second generation DAA good and bad

*Good* -Pan-genotypic -High barrier or resistance compared to other PIs -Against viral isolates with resistant mutations to 1st gen PIs -Dosed once or twice daily -Improved safety and tolerability

Midazolam for agitation/sedation

*Good* -Short on and decently short half life (shortest) of 3-11 hours *Bad* -Extensive *3A4 metbolism*, watch for DDIs -Can accumulate due to *lipophilicity and active metabolites* -Induces histamine so can cause hypotension. AVOID in septic shock

Common organisms with febrile neutropenia

*Gram Pos* -Staph epi -Staph aureus -Strep viridans *Gram Neg* -EPK *Anaerobic* -C. diff *Fungal* -Aspergillus -Candida *Viral* -Herpes simplex -RSV

Gram positive vs negative sepsis

*Gram positive* -Inflammatory process can be mediated by *exotoxin* *Gram negative* -Inflammatory process can be initiated by *ENDOtoxin w/cell lysis* -Lipid A is also highly immunoreactive

Brand names of HAV vaccines

*HAV Only* -HAVRIX -VAQTA *HAV (low dose) and HBV* -TWINRIX

Sequelae (comorbidity risk) associated with RA

*Heart Disease* -2-3X increase in CAD -2X increase in CHF *Respiratory disease* -Remember can lead to pulmonary fibrosis *Malignancy* -Lung cancer -Lymphoprolifterativee malignancies (you are suppressing the important immune system)

Red blood cell transfusion threshold in septic shock

*Hgb < 7 g/dL* EPO should NEVER be used for treatment off anemia associated with severe sepsis

TLS Treatment

*Hyperkalemia* -Kayexelate #1 -Could do calcium gluconate, insulin + dex, bicarbonate, or aggressive diuresis if wanted *Hyperphosphatemia* -Phosphate binders *Hypocalcemia* -Correct hyperphosphatemia -Calcium gluconate or carbonate *HYperuricemia* -Allopurinol 300 mg/day -Rasburicase (converts uric acid to allantoin)

IL-12 Function

*IL-12 (the boss)* -Responsible for immunologic *priming* -Activates T-helper cells to *Th1* cells that release *interferon gamma and TNF* -Interferon gamma can activate macrophages and many other immune molecules

IL-2 vs TNF action on T cells

*IL-2* -Activates T cells *TNF* -Expansion, causes T cells to proliferate and increase in number Both are needed to form a cascade that increases each other

Corticosteroids in septic shock

*IV hydrocortisone at 200 mg/day (50 Q6H)* can be considered if not adequate response to fluid resuscitation and vasopressor therapy

Entyvio (vedolizumab) clinical pearls

*IV injection ONLY* -No cases of PML reported to date (like Nate) -Preferred over natalizumab

IgM vs IgG anti-HAV antibodies in Diagnosis of HAV

*IgM +* -Denotes recent HAV infection -Disappears within 3-12 months after infection *IgG* -Means there was prior HIV infection OR immunity -Remains + and provides lifetime immunity -Measured as *total anti-HAV (IgG + IgM)

Etiology of non-hodgkin lymphoma

*Immune suppression* -HIV -Autoimmune diseases -Inherited immunodeficiency *Transplant (SOT or BMT)* -Post transplant lymphoproliferative disorder (PTLD) *Physical agents* -Pesticides -Solvent dyes *Radiation* *Infections* -Ebstein-Barr virus -Human herpes virus 8 (Kaposi sarcoma) -Hepatitis C

Clinical presentation of HebB

*Immunotolerant Phase (highly infectious(+)* -Active viral replication occurs (asymptomatic) *Immunoactive phase* -Begin having symptoms about *90 days* after HBV expoisure -Fever, anoreexia, nausea, vomiting, jaundice, dark urine, clay like pale stools, abdominal pain, *increased AST* -Significant *viremia* -Symptoms usually last *a few weeks but can last up to 6 months* or years in chronic infection *Seroconversion Phase* -HBeAg is being replaced by anti-HbeAg - infection is resolving

Pharmacokinetic changes in sepsis

*Increased freq. of:* -Hepatic dysfunction -Renal dysfunction *Increased VD!!!* -Due to rapid expansion of extracellular volume -Can lower drug levels -Consider loading doses

Aflibercept Side effects

*Increased incidence with add on regimen* -Diarreha -Asthenia -Stomatitis and ulceration -Infection *Anti-VEGF specific* -*HYPERTENSION* -Hemorrhage AND/OR thromboembolic events

Sequelae of RA

*Increased risk of death due to* 1. CV disease (2-3X increased CAD risk) 2. 2X increased risk of *CHF* 3. Disability 4. Respiratory disease 5. Malignancy - lung cancer and lymphoproliferative malignancies are more common

RISK Factors for PUD development - *KNOW*

*Independent* -NSAID use -H. pylori Most important factors in PUD recurrence -Cigarette: increases risk of ulcer and ulcer recurrence and impairs ulcer healing -Alcohol use: in high levels can cause upper GI bleed and gastric mucosa damage -Gastric acid hypersecretion -Patient nonadherence -Psychological *stress*

IL-6 Multiple Mechanisms

*Induces Many Immune Functions* -Stimulates B cell Ab production -Increases hepatocyte synthesis of CRP, fibrinogen, proteins -Increased T helper and killer cell differentiation -Osteoclast differentiation -Angiogenesis (VEGF stimulation) -Increased collagen

Tocilizumab concerns

*Induces multiple CYPs* (all the big ones) and effect can persist for weeks after stopping. In pregnancy is possible *unsafe* so avoid use usually (animal only data)

Induction and consolidation in AML

*Induction* -Goal is to achieve complete remission (blasts < 5%) *Consolidation* -Goal is to maintain complete remission (I would say also improve QOL - you use lower and less toxic chemo to keep down basically)

Pathogenesis of IBD issues

*Infectious* -M. avium paratuberculosis involved -Some E. coli spp -In IBD have higher levels of flora *Genetic* -Familial occurrence *Environmental* -Cigarette smoking can *worsen crohn's* and appears to be protective in UC -Cows milk can trigger -NSAIDs can impair mucosal barrier *Immunologic* -TNF-alpha -IL-23 -Helper T1 and T2 cells. (T1 Crohn's T2 UC)

Pathology of Invasive breast cancer

*Invasive or infiltrating ductal carcinoma* -Most common type of breast cancer (70%) and *WORST prognosis (IDC)* *Invasive or infiltrating lobular carcinoma (ILC)* -2nd most common type of breast cancer (15%) Tubular, mucinous, papillary, medullary, etc. generally have a better prognosis compared to IDC Others: adenocystic carcinoma, carcinosarcoma, papillary carcinoma, Paget's disease of breast, and inflammatory breast cancer

Ruxolitinib (Jakafi)

*JAK 1/2 Inhibitor* *Adverse effects* -Thrombocytopenia, anemia, and neutropenia (dose reduce, interrupt) -Risk of infection -Hyperlipidemia

Cetuximab and panitumumab should be use for ________________ tumors only

*KRAS/NRAS wild-type and LEFT-sided*

Who is high enough risk to receive ATG induction? (some)

*Kidney transplant* -High risk features like donor antibody, AA, etc -If lower risk you would do basiliximab *Pancreas transplant* -ALL patients get ATG *DO NOT do in liver transplant* -Trying to taper off as much as possible

Clinical TLS vs Laboratory TLS

*Lab TLS* -Occurs within 3 days before or 7 days after starting chemo -*25% change* above or below normal -For any *two or more* serum values of uric acid, potassium, phosphate, or calcium *Clinical TLS* -Presence of LTLS AND -Any one or more 1. *Creatinine 1.5 x ULN* 2. Cardiac arrhythmia/sudden death 3. Seizure

Right vs left side CRC tumors

*Left side = LONGER overall survival* (33.3 months) vs Right side tumors (19.4 months)

Tamoxifen vs letrozole side effects in the BIG 1=98 trial

*Letrozole heavy* -Hypercholesterolemia -*Joint pain* - BIG manage w/ duloxetine or SSRI -Bone fracture -Cardiac technically significant but not by much *Tamoxifen heavy - menopausal* -FLUSHING - Venlafaxine, SSRI, clonidine, gabapentin -Slightly more night sweats -Vaginal bleeding -Thromboembolic events

Leukemia vs Lymphoma

*Leukemia* -Cancer of the bone marrow myeloid OR lymphoid cells (these are WBCs) *Lymphoma* -Cancer of the lymphocytes (lymphatic system) -Cancer cells can develop in lymph organs including the the thymus, lymph nodes, bone marrow, or spleen -Involve *T cells and B cells, the lymphocytes*

Blood product admin in septic shock

*Look at platelets* -If < 10 ALWAYS give infusion -If < 20 give with significant risk of bleed -If < 50 only give with active bleed or invasive procedure

Cytarabine toxicities

*Low doses* (7+3, FLAG) -Myelosuppression -Nausea and vomiting -Diarrhea -Rash (super common) *High dose (consolidation)* -Ocular - *Conjunctivitis* - often give prophy steroid eye drops to mitigate -Cerebellar - confusion, nystagmus, ataxia - do regular neuro checks. Risk higher with renal dysfunction and advanced age - elderly are just excluded from tx usually with Hidac

Treatment options for stage II CRC *after surgery*

*Low risk* -Adjuvant chemo not recommended always -Often just observation -Could do 5-FU + leucovorin *High risk* -Observation -Possible adjuvant: 1. 5-FU + leucovorin 2. Capecitabine 3. FOLFOX 4. CapeOx 5. Flox (bous 5-FU/LV/oxaliplatin)

Empiric treatment of febrile neutropenia

*Low risk* -IV ABx once daily in clinic or at home -Oral cipro + augmentin *High risk* -Broad spectrum with cefepime, zosyyn, merrem, or imipenem/cilastin Length of treatment depends on negative cultures and resolve

Nerlynx (neratinib)

*MOA* -Binds EGFR, HER2, and HER4 *Indication* -Extended adjuvant tx of adult patients with EARLY stage HER2+ breast cancer following trastuzumab based therapy *Adverse effects* -DIARRHEA!!!! Always give loperamide around the clock. Can do colestipol if loperamide isnt working, *DDIs* -CYP3A4 substrate (MAJOR) -Inihibits Pgp

Entecavir for HBV

*MORE POTENT* than LAM and adefovir in *decreasing HBV DNA* *AVOID in HIV* unless patient is getting full HAART *Advantages* -Active in *LAM-resistant* HBV (not long term) and cirrhotic patients -Can be used for *compensated AND decompensated cirrhotic patients* *Disadvantages* -MUST take on empty stomach -Resistance can develop rapidly with prior LAM use or resistance. Low resistance with LAM naive

Hypomethylating agent pharmacology

*Mechanism* -*Cytidine* analogs -Inhibit DNA methylation by forming *irreversable* covalent adducts with *DNA methyltransferases* -Cause *re-expression of tumor suppressor genes* -Leads to differentiation and apoptosis of leukemic cells ultimately

Venetoclax pharmacology

*Mechanism* -A BCL2 inhibitor! that is ORAL! (400 mg QD) -Leukemic cells and lymphoma often overexpress BCL2, which is an *antiapoptotic protein -sequesters BIM and BAX*. In short, it allows cells to survive and is often chemo resistant. *Problem = DDI* -CYP3A4 substrate so just be careful *Side effects - well tolerated* -Myelosuppression -Diarrhea -Nausea -Fatigue

Olanzapine as an antiemetic

*Mechanism* -Blocks multiple neurotransmitters including dopamine, serotonin, catecholamines, ACh, and histamine *Metabolism* -Major by CYP1A2 minor 2D6 *Side Effects* -SEDATION -Hang over like feeling -*QT prolongation* Has super good data for efficacy in nausea and vomiting

Fludarabine pharmacology

*Mechanism* -Fludarabine is a purine analogue so kind of works in synergy against DNA with cytarabine (pyrimidine analog). It actually increases Ara-C (active form) levels -Give *4 hours prior to cytarabine to synergistically increase ARA-C activity* *Pharmacokinetics* -RENAL elimination (like cytarabine - although Cyt has mainly hepatic metabolism to Ara-U)

FLT3 Inhibitor (e.g. midostaurin, Rydapt) Pharmacology

*Mechanism* -Inhibit FLT3 (a kinase) receptor signaling to stop cell proliferation and induce apoptosis *Pharmacokinetics* -Primarily hepatic metabolism via *CYP3A4 to ACTIVE metabolites* -HIGHLY (>99%) protein bound -Long (21hr) half life with even longer half life of *active metabolite*

Cetuximab (Erbitux) + side effects

*Mechanism* -Recombinant Mab that binds to an EGFR *Side effects* -*Acneform rash (VERY COMMON)* -Headache -Feveer -Infusion reactions *KRAS mutation status may predict outcome* - mutation = NON-response. Wild-type = response

Bevacizumab (Avastin) + side effects

*Mechanism* -Recombinant human IgG1 Ab that binds to and inhibits VEGF *Side effects* -Asthenia -Headache -*Hypertension* -Proteinuria -Infusion related reactions -*Hemorrhage (BBW!)* -*Thrombosis (arterial - increased risk 2 fold)*

T-cell mediated organ rejection is treated with ______

*Moderate-severe* -High dose steroids (prednisone oral or IV methylpred) -Anti-thymocyte globulins (usually rabit) Milder rejection may respond to maintenance immunosuppression

Azathioprine and 6-MC clinical pearls

*Monitoring* -CBC at start, every 2 weeks for first 3 months, then monthly -Dose increased at 2 wk intervals *TMPT testing genotypically or phenotypically should be assessed before starting therapy*

Precedex monitoring and treatment of AEs

*Monitoring* -Vitals every 15 min for first 30 min after initiation or dose change -Then vitals every hour *Treatment* -For significant *bradycardia* consider giving *atropine* -For significant hypotension consider *fluid bolus*

Staging in NSCLC vs SCLC

*NSCLC* -Normal TNM staging (I-IV) *SCLC* -Limited vs extensive disease - SUPER SIMPLE and made by VA group -Limited: single hemithorax and can be encompassed by single radiation port - *extensive = tumor migrated outside hemithorax*

Tocilizumab side effects

*Neurologic* -Headache -Dizziness *Like most IL Antags* -URTIs -Nasopharyngitis -Opportunistic infections *Hyperlipidemia* -Increased LFTs -Injection site reactions -Increased cancer risk

CV risk assessment in PUD

*No or low CV risk* -Patient not on low dose aspirin *High CV Risk* -Patient requires low-dose aspirin AND *NSAID required* -Patient requires low-dose aspirin and *NO NSAID required*

GI bleeding risk assessment

*No or low risk* -< 65 yo and no other factors *Moderate GI risk* (1-2 factors) -Age > 65 yeasrs -High-dose NSAIDs -Concomitant use of aspirin, corticosteroids, or anticoagulants *High GI risk = > 2 risk factors OR prior ulcer or ulcer related complication* -Age > 65 years -Concomitant NSAIDs, aspirin, corticosteroids, or anticoagulants -Dual antiplatelet therapy!

Guidelines for agitation

*Non-Pharm First* 1. Maintain patient comfort 2. Frequent *reorientation* 3. Optimization of environment to maintain *normal sleep patterns* Generally propofol or precedex preferred in mechanically ventilated adults

Pathology of breast cancer

*Non-invasive* Ductal carcinoma in situ (DCIS) -*Premalignant* lesion, clustered microcalciferations on mammogram, usually curable with resection alone Lobal carcinoma in situ (LCIS) -NOT premalignant and *risk factor for breast cancer*

Steroidal vs Nonsteroidal aromatase inhibitors

*Nonsteroidal* -Anastrazole and letrozole *Steroidal* -Exemestane

Ribavirin dose adjustments

*Normal dosing* -1,000 mg if < 75 kg -1,200 mg if > 75 kg *Anemia w/o cardiac disease* -Hgb < 10 g/dL: *600 mg/day* -Hgb < 8.5 g/dL DISCONTINUE *Anemia w/cardiac Disease* -If Hgb decreases by > 2 g/dL in any 4-week period in patients WITH CD reduce dose to *600 mg/day* -If Hgb *<12 g/dL* DISCONTINUE

HBV drugs that can ONLY be used in compensated cirrhosis

*Nucleotide Analogs* Tenofovir alafenamide Adefovir

Osteoarthritis vs RA common locations

*OA* -More back and spine and hips -Knees -Distal phalanges *RA* -More feet -Knuckles more common RA can effect spine, neck, knees, and hip but is much less common

Remicade biosimilars on and off-market

*On market* -Inflectra -Renflexis *Not on market* -Ixifi All for CD, UC, and RA

Common CYP3A4 andd PGP inhibitors

*Onset is QUICK* -Erythromycin and clarithromycin -Ketoconazole, voriconazole, itraconazole, fluconazole -Non-DHPs - *diltiazem and verapamil* -Nicardipine (minor) -*Grapefruit juice*

Common adjuvant chemo regimens for breast cancer

*Oral CMF* -Cyclophosphamide, MTX, and 5-FU for 28 days X 6 cycles *IV CMF* -Cyclophosphamide (higher dose), MTX, and 5-FU. 21 on, 7 off for 6-12 cycles. May be preceded by anthracycline. *Dose dense AC-T* -Doxorubicin, cyclophosphamide, and paclitaxel. Q14d x 8 cycles. Can be *+/- paclitaxel* *TC* -Docetaxel and cyclophosphamide 21 on 7 off x 4 cycles

NSCLC Stage IV 1st line targeted therapies for *EGFR mutation*

*Osimertinib (Tagrisso)* *Erlotinib (Tarceva)* -Afatininb (Gilotrif) -Gefitinib (Iressa) -Dacomitinib (Vizimpro) Second line -Osimertinib

Targeted immunotherapies that can be used first or second line

*PD-1 inhibitors* -Atezolizumab (Tecentriq) -Pembrolizumab (Keytruda) NOT first line -Nivolumab (Opdivo) -Durvvalumab (Imfinzi) Not: these are *NOT cytotoxic* and specifically useful in NSCLC Choice of agent really depends on health system - NCCN says pebrolizumab first line if > 50% PD-1 expression

Methotrexate DDIs and PK

*Pharmacokinetics* -80% excreted unchanged in urine - tubular secretion 2.5X > glomerular filtration. So *dose reduce if CrCl < 60 mL/min* -50% plasma protein binding so caution with hypoalbuminemia *DDIs* -NSAIDs compete for tubular secretion and increase GFR increasing levels -PCN and derivatives compete for secretion -*PPIs can increase oral absorption and reduce elimination*

Key factors in innate immunity

*Physical and chemical barriers* -Skin -Cilia and mucous -

Hydroxychloroquine and pregnancy/lact

*Pregnancy* -Category D -Evidence says *generally SAFE* *Lactation* -Concerns in package insert, but is compatible with breastfeeding -No evidence of retinotoxicity or ototoxicity

ATG administration

*Premedicate!* -Methylprednisolone (1st dose only) -Acetaminophen -Diphenhydramine -Infuse over 4-6 hours through an *in-line filter via central or peripheral line* -Add *heparin and hydrocortisone in peripheral to prevent local rxn* May need to *dose reduce for low WBC/Plt and side effects*

Liver disease from TPN management and prevention

*Prevention* -Avoid LONG TERM use of TPN if possible -Avoid OVERFEEDING - long term use off excess calories is a big risk *Treatment* -Cycle PN (usually lipids only once a week or les sfrequent) -*Ursodiol* -Maximize EN -*Avoid overfeeding*

Hyperglycemia from TPN prevention and treatment

*Prevention* -Make sure Dex infusion rate is NOT >4-7 mg/kg/min -Start PN infusion slow and increase rate gradually *Treatment* -Remove all maintenance dextrose -Monitor *BG Q6H* -Start moderate dose *insulin correction scale*

Primary vs secondary humoral response

*Primary* -Usually takes 5-10 days to develop -*Initially IgM* followed by IgG - IgM and IgM in similar levels *Secondary* -Mediated by memory B lymphocytes -Primarily IgG (minor IgM) -Can be activated at very low concentrations of antigen - *REPEAT exposure*

Morphine for pain: Pros and Cons

*Pros* -Fast onset and shortish duration and elimination half life *unless in hepatic or renal dysfunction, then accumulates!* *Cons* -Risk accumulation due to *active metabolites* and in renal/hepatic dysfunction -Longest half life of IV opioids -Renally eliminated -Induces release of histamine which can lead to hypotension (not in her slides from crit care, important)

DLBCL GCB subtype treatment

*R-CHOP* -*R*ituximab on day 1 -*C*yclophosphamide on day 1 -Doxorubicin (*H*ydroxydaunorubicin) on day 1 -Vincristine (*O*ncovin) -*P*rednisone PO BID days 1-5

DLBCL GCB subtype treatment

*R-CHOP* -*R*ituximab on day 1 -*C*yclophosphamide on day 1 -Doxorubicin (*H*ydroxydaunorubicin) on day 1 -Vincristine (*O*ncovin) -*P*rednisone PO BID days 1-5 *IF DOUBLE HIT* -R-DA-EPOCH (Ritux, ETOPOSIDE, Prednisone, Vincristine, Doxorubicin) -You might not be able to use all agents -Consider doing CNS prophylaxis

DLBCL: ABC Treatment

*R-CHOP* Rituximab Cyclophosphamide -Doxorubicin (Hydroxydaunorubicin) -Vincristine (Oncovin) -Prednisone Double expressers have notably worse survival, but it does not appear there is benefit from more aggressive chemo

Rabbit (Thymoglobukin) vs Horse (Atgam) ATG

*Rabbit* -Much more POTENT (1.5 mg/kg/day) than Atgam -Longer lymphocyte depletion *Horsie* -Dose is higher because less potent (15 mg/kg/day) -Rarer use -Requires *TEST DOSE*

Dermatologic infections with EGFR inhibitors (cetuximab and panitumumab) - CRC

*Rash is very common* -S. aureus infection in grade 3/4 radiation dermatitis -EGFRi treated patients 38% with infections usually S. aureus -In oncology, SSTI can result in bacteremia with skin and mucosa entry in 64%. Associated with *16% mortality* *Study* -28% of persons tx with EGFR inhibitor had bacterial, viral, or fungal infection -Higher risk with leukopenic patieents

HepA vs B vs. C risk factors

*Related* -IVDA -Hemodialysis -Male homosexuals *HepA* -Oral-anal sexual contact *HepB* -Persons with STDs -Household contacts _Residents or staff of disabled homes *HepC* -Baby boomers -Intranasal drug users

Clinical presentation of AML

*Relatively specific* -Hemorrhage (petechiae) -Weight loss (often 20+ pounds fast with no cause) *Nonspecific* -Fever -Fatigue -Infections -Easy bruising

SOFA Score Components

*Respiratory* -High = lower resp rate. This is with resp support -PaO2 <100 worst *Platelets* -High = < 20 *Bilirubin* -High score (4) if > 12 *CV Hypotension* -High = requiring dopamine > 15 or epi > 0.1 or NE > 0.1 *CNS-Glasgow Coma Score* -Low score = bad *Renal - Creatinine* -Highest score = BAD

Non-small cell lung cancer (NSCLC) - 85% of all lung cancers

*SQAMOUS cell carcinoma* -30% of NSCLC -More common in *smokers and MALES* *Adenocarcinoma* -50% of NSCLC -Cancer begins in cells that line *alveoli* -Most common in *NONsmokers* + women > men *Large cell carcinoma* -Cancer that may begin in several types of large cells, *slow growing*

PD-1 inhibitor Side effects

*STIMULATING of immune system* -Diarrhea (can become colitis) -LFT abnormalities -Hypothyroidism -Rash -Hypophysitis (acute pituitary inflamm) -Nephritis -Adrenal suppression -Uveitis -Arthralgias/myalgias -Faitigr *Immune-related Adverse Events (irAEs)* are NON-CYTOTOXIC, but can still be toxic. Most toxicity manifests as *inflammatory-like side effects*

Metoclopramide side effects

*Sedation* *Diarrhea* Dizziness EPS *QT prolongation*

Breast examination recommendations (ACS)

*Self-Examination* -*Monthly* the week after menses -ALL women *>20 years old* -Has NOT demonstrated ANY benefit *Clinical Exam* -Annually recommended (especially > 40 yo) -NOT studied as independent screening *Mammography* -ANNUAL screening reduces mortality from breast cancer in *WOMEN > 50 yo* -Questionable benefit in women 40-49 years

New ACCP/SCCM definition of septic shock

*Sepsis with:* -Hypotension NOT responsive to fluids -Serum *lactate > 2 mmol/L* -Need for *vasopressors* to maintain *MAP > 65 mm Hg*

Cyclosporine and tacrolimus side effects

*Shared* -*Nephrotoxicity HUGE* -Hyperkalemia -Hypomagnesemia -Hypertension -Neurotoxicity (*Tremor*, *headache*, confusion, seizure) *Cyclosporine* -Hyperlipidemia -Hyperuricemia -Hirsutism (hair GROWTH) -Ginigval hyperplasia *Tacrolimus* -Hyperglycemia (new onset *diabetes*) -Alopecia -*Diarrhea* - because of PK of drug

Etiology of lung cancer

*Smoking* -Attributed to 80% of lung cancer deaths -Spouses have 25% higher risk of lung cancer than spouses of non-smokers -Environmental (e.g. asbestos, other toxins) -Genetics -COPD -*Adults with asthma*

Cyclophosphamide specific side effects

*Specific* -Cardiotoxicity -Pulmonary toxicity -INFERTILITY *Nonspecific* -Myelosuppression -Secondary malignancies -Mucositis -Neutropenia -Fever -Alopecia -N/V -Diarrhea

Etoposide adverse reactions

*Specific* -Hypersensitivity reactions and *hypotension* due to excipients in formulation *Nonspecific* -Myelosuppression -Secondary leukemia -Mucositis -N/V

Vincristine (Oncovin) toxicities

*Specific* -Neurotoxicity (NEVER give intrathecal can cause death) -Peripheral neuropathy and neuralgias -CONSTIPATION (can be big issue) *Nonspecific* -Edema -Alopecia

Step up vs Top down therapy and the clinical controversy

*Step Up Advantages* -Attain remission with less toxic drugs -Reserve more toxic therapies for more severe -Save Money *Top Down Advantages* -Biologics are immunogenic -CAN alter disease course *Step Up Disadvantages* -Decrease QOL before patient obtains an optimal therapy (take time!) -Higher chance of surgery need -Disease is *not modified* *Top Down Disadvantage* -Cost -No benefit with steroid induction -No difference in short or long term responses to induction/maint refractory -Increased long term toxicity

Precipitating risk factors for delirium

*Strong Evidence* -*Mechanical ventilation* -Metabolic disturbances *Weaker evidence* -Infection -Hypovolemia -Hypo or hyperthermia -Restraint use -Hypoxia -Sleep deprivation -Hemodynamic instability -Uncontrrolled pain -*Medications: anticholinergics, antihistamines, benzos, opioids, steroids*

Predisposing risk factors for delirium

*Strong evidence* -Age -Dementia -HTN *Weaker evidence* -*Polypharmacy* -Depression -Anemia -Malnutrition -Alcohol use -Renal faiure -Liver disease -Intractable pain -Tobacco use -Visual and hearing loss -CHF

Treatment of colon cancer

*Surgery* -Stage I-III: Curative intent -Stage IV, resectable disease: *Curative intent: unique w/stage IV colon caner* -Stage IV, unresectable: Palliative *Radiation* - palliative *Chemotherapy* -Stage II: Adjuvant chemo controversial -Stage III: Adjuvant chemo -Unresectable stage IV: Palliative

Acute HAV signs and symtptoms

*Symptoms* -Abrupt and nonspecific in preicteric phase -Worsening systemic symtoms in icteric phase *Signs* -Jaundice -Increased LFTs

Stage IV breast cancer treatment

*Systemic therapy* -Chemotherapy -Endocrine therapy Goal: Palliation, prolonging life, maximizing QOL - cure unlikely

TDF vs TAF

*TDF* -May have risk of renal and bone toxic effects due to high plasma tenofovir levels but still LESS nephrotoxic than adefovir *TAF* -Improved renal and bone safety -Recommended over TDF IF the patient has risk or current bone disease: includes *chronic steroid use, history of fragility fracture, or osteoporosis*

Paclitaxel dosage forms (Lung cancer)

*Taxol* Cremophor EL (polyoxyethylated castor oil) -Thought to be responsible for *hypersensitivity (need to premedicate) and neurotoxicity* -*Paclitaxel usually infused first when given with other chemo* -Has less timor penetration -Long infusion times needed AND special infusion sets -Dose is lower than abraxane *Abraxane* -Nanometer albumin bound -*NO HYPERSENSITIVITY* (no need to premedicate) -Increased tumor penetration -*Fast 30 min infusion time* -Does NOT need special infusion sets -Dosed HIGHER than Taxol

Lorazepam for agitation (not really used now)

*The bad* -LONG half life of 8-15 hours -Renal and hepatic elimination, so risk accumulation due to decreased organ function *Good* -NO active metabolites

Day *1* Prophylaxis for MODERATE emetogenic risk chemo

*Three options similar to HIGH risk* 1. 5-HT3 antagonist + dexamethasone +/- NK1 antagonist 2. NK1/5-HT3 antagonist + dexamethasone 3. Olanzapine + 5-HT3 antagonist + dexamethasone *IF a patient has N/V after 1st cycle OR high risk features, consider adding on prophy with substance P/NK1 receptor antagonist*

Shared tacro and cyclosporine adverse effects

*Top* -Nephrotoxicity -Hyperkalemia -Hypomagnesemia -Hypertension -Neurotoxicity (tremor, HA, confusion, seizure)

When would you use naloxone or SQ methylnaltrexone to treat intestinal hypomotility?

*Tx Refractory* -First line agents like docusate, PEG, miralax, etc not working -Tried bisacodyl or some enema and not working

Treatment of DCIS - Remember DCIS is pre-malignant

*Tx focused on preventing development to breast cancer* 1. Surgery -Lumpectomy + radiotherapy OR -Total mastectomy +/- reconstruction w/ lymph node dissection 2. Tamoxifen should be considered if ER/PR+

Mesalamine indications

*UC ONLY* - induction AND maintenance of remission

Simponi (golimumab) indications in IBD

*UC ONLY* - induction and maintenance of remission in patients with mod-severe failing conventional *or requireing chronic steroids*

Topical hydrocortisone indications

*UC ONLY* for induction to remission of rectal, sigmoid, and/or left colon disease Cortenema Cortiform Anusol-HC

Bismuth formulations MOA and peals for PUD

*Ulcer healing* via multiple mechanisms -Antibacterial -Local gastroprotective -Simulates endogenous PGs DOES NOT inhibit or neutralize acid *CAUTION: Bismuth use in older patients or renal failure* Bismuth can cause black colored stool and tongue Long term use not recommended

Diagnostic differences in UC versus CD

*Ulcerative Colitis* -Bleeding is very frequent (mucosa inflamm) -Mucosal inflammation -Goblet cell depletion -*Crypt abscess* -*Superficial ulcer* -Upon barium contrast *Rectal involved* and superficial ulcers *Crohn's* -May have bleeding (less common) -Transmural inflammation -DEEP ulcer -Fissuring or granulomas -Patchy involvement -Upon barium contrast *rectal spared*, mucosal infolding, *fistulas*, and extraluminal striction

Crohn's vs UC

*Ulcerative Colitis* -Inflammation of *musosa* -Usually have *ulcers* in *lower part of large intestine (colone/rectum)* *Crohn's* -Transmural (all layers of gut) inflammation -*Ulcers in patches* that can affect any part of the GIT

Sirolimus (Rapamune) and Evverolimus (Zortress, Affinitor) mechanism

*mTOR inhibitors* -Block the downstream signaling after IL-2 binds to its receptor -Inhibits cell proliferation and can be used as alternative to calcineurin inhibitor. Also another option in place of mycophenolate.

Rituximab warnings and precautions

- Know that nephrotoxicity concern is IRRELEVANT in RA it is for TLS with cancer - *CV reactions are rare, but serious* -*PML risk due to JC virus* -Pregnancy cat C, but manufacturer recommends contraception for *1 year after last dose* -For lactation manufacturer recommends delaying until *6 months after last dose* Medicolegal implications of defying manufacturer instruction

Risk factors for NSAID induced PUD

-*Age > 65* -Prior *peptic ulcer hx* -Previous ulcer related upper GI probs -*High dose* NSAIDs -Multiple NSAID use -*Selection of NSAID - nonselective worse* -NSAID related dyspepsia -Aspirin (even at low dose) Concomitant use of: -NSAID + ld aspirin -Oral bisphosphonates -Corticosteroids -Anticoagulant or coagulopahty -Antiplatelet drugs -Selective serotonin reuptake inhibitor -Chronic debilitating disorders like CV disease or RA -H. pylori infection -Cigarette smoking -Alcohol consumption

NSCLC Stage IV 1st line targeted therapies for *ALK mutation*

-*Alectinib (Alecensa)* -Ceritinib (Zykadia) -Crizotinib (Xalkori) Second line FYI -Alectinib -Brigatinib (Alunbrig) -Ceritinib -Lorlatinib (Lorbrena)

Postmenopausal adjuvant endocrine therapy for breast cancer

-*Aromatase inhibitors first line* -Tamoxifen Why aromatase 1st? - *BIG 1-98 trial* -Showed increased disease free survival with letrozole vs tamoxifen -More bone fractures and grade 3-5 cardiac events in letrozole group -Letrozole std for most ER+ early breast cancer patients

NSCLC Stage IV 1st line targeted therapies for *ROS1 rearrangement*

-*Crizotinib (Xalkori)* -*Entrecitinib (Rozyltrek)* Other FYI -Ceritinib -Brigatinib -Lorlatinib

NSCLC Stage IV 1st line targeted therapies for *BRAF600 mutation*

-*Dabrafenib (Tafinlar) and trametinib (Mekinist) COMBO drug* Other FYI -Vemurafenib -Dabrafenib

Irinotecan side effects

-*Diarrhea* -N/V -Neutropenia -Fatigue -Alopecia Moderate emetogenic risk score *Early onset diarrhea* -Give atropine 0.25-0.5 mg IV. Due to cholinergic surge from inhibition of AChE *Late onset diarrhea* -Give intensive loperamide. 4 mg at 1st onset then 2 mg Q2H until diarrhea free for 12 hours. NO MAX

Baricitinib (Olumiant) clinical pearls

-*GI perforation* increased with *NSAID use* (Like xeljanz) -AVOID in pregnancy and lactation (like xeljanz)

Regorafenib (Colorectal cancer, VEGF) toxicities

-*Hand foot syndrome* -Fatigue -*Hypertension (like all VEGF)* -Rash -*Anorexia* -Oral mucositis -*Thrombocytopenia*

Hydroxychloroquine side effects

-*Irreversible retinal damage* - eye exam at baseline and annual monitor after 5 yrs -Cardiotoxicity - *QT prolonging* -Myopathy -*Psychiatric events* - anxiety, insomnia, nightmares, psychosis

NSCLC Stage IV 1st line targeted therapies for *NTRK gene fusion*

-*Larotrecitinib (Vitrakvi)* -*Entrecitinib (Rozyltrek)*

Calcium-phosphate preciptiations problems

-*Lower solution pH = more soluble*. Amino acid products often contain phosphate and increase pH of solution, so be careful -*Calcium gluconate* preferred due to lower dissociation and less free Ca -*Longer time = increased risk of ppt*. Expire after 24H -*Increased temperature is BAD: Increases free Ca and phosphate, therefore more ppt* -MUST *separate Ca and PO4* when compounding. Usually phos first then everything then Ca last

Microsatellite Instability

-*MMR protein testing* on cancer specimen is recommended -If immunohistochemical analysis reveals absence of *MLHI protein expression* recommend *BRAF gene mutation testing* to distinguish between somatic and germline MLH1 mutation -Individuals with abnormal MMR protein expression or MSI should be referred for genetic counseling *Patients with MSI-H DO NOT gain survival benefit from 5-FU* and may require combo therapy in adjuvant setting.

Ixabepilone (Ixempra) for breast cancer

-*Microtubule inhibitor* -Approved s/p failure with anthracycline and taxane +/- capecitabine -*Premedicate with H1 and H2 antagonist* -Hypersensitivity rxns -Neuropathies -Myelosuppression *Note: CYP3A4 substrate*

5-FU side effects

-*Mucositis* and stomatitis -*Diarrhea* -N/V -*Neutropenia* -Neurotoxicity -Skin reactions -Alopecia -Evlevated ALTs *Prevention* -Preveent oral mucositis with *ice chips* and proper oral hygeine -Treat diarrhea with *loperamide or Lomotil* (new data on octreotide)

Kevzara (sarilumab) adverse effects

-*Neutropenia* -Infection -Transaminitis -Dyslipidemia -Injection site reactions and erythema

Dopamine receptor antagonist side effects

-*Orthostatic hypotension* -*Excessive sedation* - less with Tigan -EPS -*QT prolongation* (NOT tigan)

Plaquenil big side effects to consider

-*Ototoxicity (tinnitus)* -*Retinal toxicity* - IRREVERSIBLE -*N/V/D* -*Cardiotoxicity* - QT prolonging too -Myopathy -*PSYCHIATRIC events* - anxiety, insomnia, nightmares, and psychosis

NSCLC Stage IV 1st line targeted therapies for *PD-L1 expression*

-*Pembrolizumab (Keytruda) alone IF PD-L1 > 50%* -*Keytruda + PEMETREXED + carboplatin or cisplatin* for NONsquamous PD-L1 < 50%) Other FYI -Carboplatin + paclitaxel + bevacizumab (Avastin) + atezolizumab (Tecentriq) (nonsquamous) -Pembrolizumab + paclitaxel or nab-paclitaxel + carboplatin or cisplatin for SQUAMOUS 2nd line FYI -Atezolizumab -Nivolumab -Pembrolizumab -Single agent chemo

NS5B (-busvir) inhibitor MOA

-*Polymerase inhibitors* that bind to NS5B active site resulting in *chain termination* and increased errors when incorporated into RNA chain growth *Nucleoside/nucleotide inhibitors* -Pan-genotypic -BAD: Highest barrier to resistance *Non-nucleotide inhibitors* -GT1b > GT1a -GOOD: Low barrier to resistance

Haldol ADEs

-*QT prolongation* -Neuroleptic syndrome -EPS -Lowers seizure threshold

Sulfsalazine pros

-*Shorter onset* of action than HCQ -Safe in pregnancy (safest)

Where do we generally want someone to be on the RASS sedation score

-1 or -2 Can get attention easily with voice, but not fully awake

Antiemetics that effect visceral tissues in stomach

-5-HT3 antagonists -5-HT4 agonists (metoclopramide)

When do symptoms typically begin after HepB infection

-90 days after exposure

Obinutuzumab (Gazyva)

-A CD20 targeted antibody like rituxumab, but glycoegineered to basically be more potent 1. Increased direct cell death 2. Increased ADCC 3. Lower CDC (complement dependent)

IL-10 function

-A regulatory interleukin that *inhibits T cell activity* -Suppress macrophages and CTL, B cell growth factor

Xeljanz (tolfacitinib) indication for RA

-AFTER failing MTX indication -Guidelines recommend trying after failing *2 TNFi AND 2 N-TNFi agents*

Who gets treated for HCV?

-ALL HCV infected *HCV RNA (+) AND biopsy (+) chronic hepatits, bridging fibrosis* Exception: Limited life expectancy *URGENT tx of patients with advanced fibrosis or compensated cirrhosis*

Epclusa (velpatasvir/sofosbuvir) clinical pearls

-ALL sofosbuvir points -Ok in ALL stages of renal impairment and HD -Not recommended with drugs that are *inducers of PGP and/or moderate to potent inducers of CYP2B6* (can decrease effect) -Medications that *INCREASED gastric pH will likely decrease VEL concentration- not recommended to co-admin with PPIs unless medically necessary* -Administer VEL/SOF *with food 4 hours before omeprazole (max 20 mg)* -With *H2RA admin WITH or 12h apart from VEL/SOF* (NOT to exceed doses equivalent to famotidine 40 mg BID -Separate *VEL/SOF and antacid by 4 hours*

When would you hold valganciclovir of ganciclovir for CMV treatment? What are monitoring parameters of CMV treatment?

-ANC < 500 -PLT < 25,000 -Hgb < 8 *Monitor* -SCr for dosing -Symptoms for end organ damage -CMV-PCR at *>/= 2 weeks induction* -Ganciclovir resistance genotyping if no or slow clinical response (UL97 or UL54 mutations)

Chronic tx ONLY drugs for IBD

-AZA -6-MP

Non-TNFi biologics for RA

-Abatacept (Orencia) -Tocilizumab (Actemra) -Sarilumab (Kevzara) -Rituximab

Verzenio (abemaciclib) side effects

-Abdominal pain -Decrease in appetite -N/V -*Diarrhea after starting - median 7.5 DAYS* -Anemia -Leukopenia -Neutropenia (*maybe less than others*) -ALT/SGPT level increase -*False SCr increase* *MORE POTENT vs CDK4*

How long does HBV survive out of body?

-About 1 week

IgM Antibody

-About 10% of Ig pool -FIRST to be produced in *early response (in BLOOD)* -Very effective in killing bacteria and activating complement system M for Microbes in blood

Leukocytes (WBCs)

-Accessory cells that *activate lymphocytes, carry out phagocytosis, and secrete effector molecyles* *Consist of:* Accessory Cells (80%) 1. Neutrophils (50-70%) 2. Monocytes aka macrophages (1-6%) 3. Eosinophils (1-3%) 4. Basophils and mast cells (< 1%) Lymphocytes (20%) 1. B cells (40% circulating lymphs) 2. T cells (60% circulating lymphs) 3. Natural killer cells

EGFR Activating Mutations in NSCLC

-Activating mutations are associated with a significantly better prognosis and these patients are generally highly responsive to EGFR TKI therapy (osimertinib, erlotinib, gefitinib, afatinib) Note: Activating mutations are more common in NEVER smokers, women, and asians

Meperidine limitations

-Active metabolite accumulation in renal tox -Neurotoxic, including *seizures* -Rare use out of OR

Treatment indications for PUD

-Acute PUD (gastric or duodenal) -Gastric MALT lymphoma -Post-gastric cancer endoscopic resection -Uninvestigated dyspepsia *All if positive H. pylori test too!*

Risk factors and clinical criteria for tumor lysis syndrome

-Acute leukemia - WBC > 25,000 -Burkitts lymphoma - LDH > 2X ULN -High grade NH lymphoma - acidic urine -Bulky disease within kidney and ureters - volume depletion BUN:SCr > 20:1 -Small cell lung caner - preexisting renal dysfunction -Germ cell cancer - baseline uric acid > 7.5 mg/dL

*KRAS* wild-type therapy for CRC stage IV

-Add on cetuximab or pamitumumab

Nephrotoxic antiviral for ABV

-Adefovir

What drug should be combined with lamivudine for compensated cirrhosis?

-Adefovir

Which HBV antiviral probably has the most clinically significant nephrotoxicity?

-Adefovir dipivoxil (ADV) Reported at higher doses of 30 mg/day, however the lower dose at 10 mg is as effective as placebo

Normally nourished/well nourished classification definition

-Adequate or minimal change in dietary intake -Minimal or no hx of anorexia -Vomiting or diarrhea *< 2 weeks* -Weight change *< 5% of UBW*

Corticosteroids in septic shock

-Adrenal insufficiency can often occur in septic patients -Corticosteroids are VERY CONTROVERSIAL in septic shock

Prednisone and hydrocortisone adverse effects

-Adrenal suppression -Growth failure -Osteopenia -Osteoporosis -Edema -Hisutism -Hyperglycemia -Impaired wound healing and infection -Altered body shape -Psychosis -Cataract

Risk factors for colorectal cancers

-Age -Environment -Hereditary (*1st degree*) - 20% -Obesity/diet (red and processed meats) -IBD (e.g. UC or Crohn's) -Prior colorectal cancers, colorectal adenomas, or pelvic irradiation -Personal history of *ovarian cancer* -Cigarette smoking -*Alcoholism* -*African America*

High risk factors for chemo related nausea and vomiting

-Age (very old or young) -N/V during prior chemo experience -History of morning sickness during pregnancy -FEMALE -History of motion sickness

Screening for persons with polyps at prior colonoscopy

-Age of screening dependent on number and grade of dysplasia, 3-10 years after polypectomy -*Recommend colonoscopy every 5 years*

Hyperactive symptoms of delirium

-Agitation -Combative behaviors -Progressive confusion MORE OBVIOUS

Cyclophosphamide pearls (for RCHOP)

-Alkylating agent that cross links and decreases DNA synthesis, cell cycle nonspecific -PRODRUG activated in liver -Remember *acrolein* metabolite that causes hemorrhagic cystitis - can give MESNA and *IV rehydration* to prevent

Who should be vaccinated for HAV?

-All children at 12 months (12-23 months) -Adults at risk Two doses (except TWINRIX) to ensure long term immunity - minimum interval of 6 months between 1st and second

Harvoni (ledipasvir + SOF) clinical pearls

-All concerns same with SOF -OK in all stages of renal impairment and HD -Medications that *INCREASED gastric pH will likely decrease VEL concentration- not recommended to co-admin with PPIs unless medically necessary* -Administer VEL/SOF *with food 4 hours before omeprazole (max 20 mg)* -With *H2RA admin WITH or 12h apart from VEL/SOF* (NOT to exceed doses equivalent to famotidine 40 mg BID -Separate *VEL/SOF and antacid by 4 hours*

Amino acid solution consideration

-All contain balance of essential, conditionally essential and nonessential AAs -Also *contain electrolytes that must be considered* - often phosphorous. Must look at product info

Things that result in high risk for febrile neutropenia

-Allo HSCT -Acute leukemia -Anticipated prolonged neutropenia -*Alemtuzumab* (Anti-CD52 immune system wipeout) -*GVHD on high dose steroids*

HAV vaccine response

-Almost all people will develop protective antibody levels *within 1 month* of first dose

Phenylephrine key PD points

-Alpha agonist only -Least likely to produce tachycardia

Lamivudine for HBV

-Also active in HIV, but must be part of HAART therapy and MUST get *higher HIV dose* *Advantages* -Good safety profile -Normal *ALT levels over 3-6 months* -Can be used in compensated *and decompensated* cirrhotic patients but *MUST combine with adefovir or tenofovir - the tide* *Disadvantages* -HBeAg (-) treatment duration and serum HBV DNA return to baseline after DC -58% relapse rate -Increased resistant rates with every year of therapy -There are confirmed *LAM-resistant mutations* - change to agents with activity against LAM resistance

Humira biosimilars made but not available

-Amjevita -Cyltezo -Hyrimoz

Basic extraintestinal manifestations of IBD

-Anemia -Bone disease (supplement Ca and VitD) -Stomatitis -Kidney issues (UTI, stones) -Skin lesions -*Arthritis* -Increased risk of *DVRT/VTE*

Balsalazide (colazal) clinical pearls

-Another azo-bonded prodrug formulation of mesalamine -Better tolerated than sulfsalazine Essentially no different than olsalazine

Preferred chemo regimen for node positive breast cancer patients

-Anthracycline and taxane based regimens So NOT CMF AC then Paclitaxel (AC-T) improved survival in node+ breast cancer patients

Pharmacology of AZA and 6-MP

-Anti-inflammatory and immunosuppressive 6-MP undergoes extensive *first pass by XO to 6-TU acid* and is excreted by kidneys so caution with XO inhibitors TMPT genetics or phenotyping must be done because MP is converted to active metabolite *6-MMP by TPMT* IMPDH also converts to 6-thioguanine, which is an active metabolite that causes *bone marrow suppression*

Acneiform rash prevention

-Antibiotics (usually minocycline or doxycycline) -Moisturizers and sunscreens like hand-foot

Antiemetics that work on the vomiting center in stomach

-Antihistamines -Anticholinergics -Metoclopramide

When can rejection of an organ transplant occur?

-Any time after transplant, but more common in the first few months

Antiemtic for LOW emetogenic potential chemo

-Anything EXCEPT *substance P/NK1 antag* Usually: 1. Zofran 8 mg 2. Compazine 10 mg

Hypoactive delirium s/s

-Apathy (calm and lethargic) -Inattention -Decreased mobility -Obtundation -Confusion and sedation characterizes

Hypoactive delirium symptoms

-Apathy (lack of enthusiasm) -Inattention -Decreased mobility -Obtundation (lack of awareness)

Symptoms of RA

-Arthralgia and stiffness *> 6 weeks* of insidious (subtle) onset *+/- fatigue* -Low-grade *fever* -Hypophagia -Myalgia -Frank deformity in later stages -Symptoms usually *worse at rest* and especially *upon wakening* and may lessen with use

Things that decrease risk of colon cancer

-Aspirin -NSAIDs -Estrogen supplementation -Physical activity -*Multi-vitamin with folic acid*

PD-L1 inhibitors

-Atezolizumab (Tecentriq) -Durvalumab (Infinzi)

Familial adenomatious polyposis

-Autosomal dominant colorectal cancer -0.5% of all colorectal cancer -Adenomatious polyposis coli (APC) gene is on long arm of *chromosome 5, 5q21* -Characterized by hundreds of thousands of *tiny adenomatous polyps that carpet colum and rectum* -Arise during adolescence and *evident by age 25* DO a TOTAL colectomy when polyps are detected

Hereditary nonpolyposis or *Lynch syndrome*

-Autosomal dominant passed down disease with early age on onset (median 46 years*) -2-4% of all colorectal cancer *Lynch I* -Absence of estracolonic neoplasms *Lynch II* -Extracolonic neoplasms including ovary, breast, endometrial, gastric, and bile duct Pathogenesis linked to mutations in mismatch repair genes

Tenofovir alafenamide precautions and contraindications

-Avoid in CrCl < 15 mL/min and NOT receiving HD -Avoid in child-pugh B or C -In HD patients, administer *after HD* -Strong *PGP and BCRP inhibitors* may effect TAF absorption *Contraindicated with PGP and BCRP inducers - phenytoin, st johns wort*

Mesalamine clinical pearls

-Avoid in salicylate allergy -3% have *paradoxical worsening* of colitis symptoms *Delzicol and Asacol HD formulations NOT interchangable* -Asacol is no longer available on market - DELZICOL replaced. Can use asacol HD, but NOT interchangable as stated above.

Sulfsalazine clinical pearls

-Avoid with sulfa or aspirin allergy -20-25% of patients will DC due to side effects -*Sulfapyridine responsible for most AEs* *Anemia Tx* -Due to impaired folic acid absorption and folate deficiency -Give folic acid 1 mg/day in ALL patients *GI and nervous system side effects or mild heme tox* -Treat by *dose reduction&* to 2-4 g daily *SAFEST DMARD IN PREGNANCY* *Worsens porphyria* (porphyrins needed for Hgb production) Counsel on *HYDRATION* to reduce the risk of nephrolithiasis and AKI

Olsalazine (Dipentum) clinical pearls

-Azo-bonded prodrug formulation of mesalamine -*Better tolerated than sulfsalazine* - similar to mesalamine

BCL6 and DLBCL

-BCL6 helps to regulate BCL2 (antiapoptotic) and MYC (increases cell proliferation) expression -Abnormalities on BCL6 can dysregulate BCL2 and MYC

What are commonly used surrogate markers of pain that are actually POOR diagnostically?

-BP -HR These are sensitive, but NOT really specific

Lab monitoring for TLS

-Basic metabolic panel -Uric acid -Phosphorous -LDH Monitor *Q12H* *Usually stop TLS labs by day 10*

Fluid resuscitation guidelines in sepsis

-Begin ASAP with either crystalloid or colloid *30 mL/kg of IV crystalloid START IMMEDIATELY and complete within first 3 HOURS for sepsis induced hypoperfusion* If lactate > 4, resuscitation should be guided to normalize lactate

Antimicrobial therapy in septic shock

-Begin IV Abx within *fist hour of recognition of sepsis* -Consider possible pathogens, site of infection/source control, etc. -Reassess regimen 48-72 hours after initiation

Abatacept and belatacept MOA

-Bind directly to *CD80/86* on APCs to prevent the co-stimulation and activation of T cells

Abatacept (Orencia) and belatacept (Nulojix) MOA

-Bind directly to *CD80/86* on APCs to prevent the co-stimulation and activation of T cells -Belatacept is about 4X as potent as orencia

Basiliximab MOA

-Bind to the IL-2 receptor and inhibit T cell activation -*IL-2 receptor antagonists*

Rituximab MOA

-Binds to CD2- on B cells and results in *antibody-dependent cell mediated cytotoxicity (ADCC) AND complement activation* Ultimately leads to apoptosis or lysis of the B cells

Propofol MOA and properties

-Binds to GABAa receptor complex *The Good* -Hepatic metabolism via glucuronidation -Onset is quick and half life is short -Can produce light or deep sedation *The Bad* -Depresses hypercarbic and hypoxemic drives of ventilation hence *need a ventilator* for continuous infusion -Causes *hypotension and bradycardia* so there is concern for worsening -Oil in water emulsion, can increase infection risk (however does provide some calories) -monitor TGs -*NO ANALGESIC PROPERTIES*

Ipilimumab MOA

-Binds to and blocks CTLA4 on T cells -No CTLA4 means no suppression of immune response

Tocilizumab MOA

-Binds to the IL-6 *receptor* interfering with normal IL-6 signaling

Anthropometic measurements for nutrition assessment

-Body weight classification -Height -BMI

Inducers of CYP3A4 and PGP

-Both lower CsA, TAC, SRL, and ERL levels *Max effect occurs after 7-10 days* *Examples:* -Rifampin -Phenytoin -Phenobarbital -Carbamazepine -Nafcillin -St. John's Wort

IL-12 and IL-23 functions in the body

-Both share the same subunit and are proinflammatory, activating the JAK/STAT pathway -Both are essential in *gut homeostasis, especially IL-23* *Th Cell* -Th1 is driven by IL-12 -Th17 is driven by IL-23

Antiemetics that hit the cortex

-CB1 agonists -Benzodiazepines

Sulfsalazine monitoring

-CBC and LFTs at initiation and *every 2 weeks* during *first 3 months* - then monthly Counsel on importance of *hydration* to reduce risk of nephrolithiasis and AKI

Ketorolac and ibuprofen limitations

-CI in active bleed (GI or otherwise) -Caution in renal dysfunction -Caution with PLT abnormalities -Caution with ACEis

Special needs for Zepatier

-CI with OATP1B1/3 inhibitors, strong 3A inducers, and efavirenz -Gentotype 1a: Test for NS5A resistance associated polymorphisms -*ALT elevations - perform hepatic lab testing prior to therapy at week 8* -Monitor for myopathy with statin - lowest necessary simvastatin dose should be used

To have CMV disease diagnosis you must have? (3 things)

-CMV DNA (viremia) -Symptoms (+/- end organ damage)

Virtual colonoscopy (CTC) with CT scan

-CT scan used to visualize the entire colon and rectup -Can detect polyps and lesion density and location

Simponi (golimumab) clinical pearls

-Can be administered as IV infusion for RA, NOT indicated for IBD -Infusion reactions with IV can occur - generally mild rash

Ketamine potential advantage for pain management

-Can be used adjunct to opioids and might decrease doses required for managing pain

Why is olanzapine often an agent of choice if you are going to use an AA for delirium treatment

-Can give SQ -Probably least QT prolongation -Sedating

Second line therapy for lung cancer after failing carboplatin or cisplatin regimen

-Can use *single agents or Pt analogue combo* -Docetaxel (superior to other agent) - first though -Pemetrexed (similar response to docetaxel, but less toxic) OR -Alternate targeted agent (with specific mutations)

Capecitabine stage IV regimen

-Cape 2500 mg/m2/day administered *twice daily for 2 weeks* followed by *1 weeks rest*

Dxmedetomidine mechanism and properties

-Central alpha-2 agonist with *some analgesic properties* *The good* -Does NOT produce a deep sedation -Does *NOT depress respiratory drive - can extubate patient still on* -Short onset and short half life, although slightly longer than propofol *The bad* -Dose limiting *hypotension and bradycardia* mediated via *parasympathetic activation* -Hepatic metabolism by CYP2A6 - possible DDIs Precedex is a great option for patients who are *likely to be extubated in the next 48 hours* as an agent to spare intubation

Vomiting trigger zones in the brain

-Cerebral cortex -Chemoreceptor trigger zone -Vestibular center -Peripheral receptors (vagal. splanchnic)

Vomiting trigger zones

-Cerebral cortex -Chemoreceptor trigger zonee -Vestibular center -Peripheral receptors (vagal, splanchnic)

*Squamous* cell NSCLC initial therapy of choice

-Chemo (double) with *Keytruda* is preferred if good performance status -NCCN: Offer Keytruda PLUS Carboplatin PLUS Paclitaxel or albumin-bound paclitaxel if good performance. Chemotherapy (2 drugs) containing *carboplatin or cisplatin* if did not tolerate immunotherapy or contraindicated (e.g. poorer performance status)

Stage IIIB NSCLC treatment options

-Chemotherapy PLUS radiation (various different modalities - can be concurrent or separate) -*Durvalumab (Infinzi) immunotherapy if unresectable*

H. pylori induced PUD features

-Chronic -More *dependent on gastric pH* -Usually *epigastric pain* (NSAID or SRMD usually asymptomatic) -*Superficial ulcers* -GI bleeding is less severe, single vessel

Ulceris site of action

-Colon Rapid onset

Orencia (abatacept) admin counseling points

-Comes as syringe or auto-injector -*DO NOT RUB injection site* it speed absorption

SAFE Trial for fluid resuscitation in septic shock

-Compared *albumin vs NaCl* resuscitation *Results* -No sig difference -Insignificant decrease in mortality rates with use of colloid in a subset analysis of septic patients

Inotropic therapy option for septic shock

-Consider *dobutamine* to give "extra boost" *Indication: Continued hypoperfusion despite meeting volume and MAP goals*

HCQ in pregnancy and lactation

-Considered generally SAFE in pregnancy -*Compatible* with breastfeeding - no evidence of retinotoxicity CAUTION: Single dose *fatality has been reported in infants*

Ibrance side effects

-Constipation -Decreased appetite -Diarrhea -N/V -Anemia, leukopenia -*NEUTROPENIA* hence infections -Thrombocytopenia -Alopecia, rash -Peripheral neuropathy

Kisqali (ribociclib) side effects

-Constipation or diarrhea -N/V -Leukopenia and -*Neutropenia*, hence infections and 21 on 7 off regimen -Alopecia (more thinning), pruritis -*QT prolongation*, sudden cardiac death, cough

Vasopressin PD

-Constricts vascular smooth muscle via *V1 receptors* -Can also increase BP possibly by *inhibition of smooth muscle NO production*

Acute tx ONLY drugs for IBD

-Corticosteroids -Tacrolimus

Clinical presentation of lung cancer

-Cough -Hemoptysis -Dyspnea -*Chest, shoulder, and arm pain* (in Horner syndrome usually squamous due to tumor pressing on brachial plexus) -Wheeze -*SVC syndrome* (blood flow through superior vena cava blocked) -Pleural effusion or pneumonitis -Dysphagia -*Bone pain* -*Liver dysfunction* -*Spinal cord compression* -*Weight loss* -*Hypercalcemia in SCLC* (Squamous cell carinoma too - secrete PTH peptide and see low PTH but hypercalcemia)

Counseling points and clinical pearls for RA

-Counsel on importance of *smoking cessation* -*Renal injury* is frequently iatrogenic (caused my medical treatment) in RA

Remicade indications in IBD

-Crohn's induction AND maintenance for mod-severe disease failing conveentional -UC induction AND maintenance *and mucosal healing* for same as above

Risk factors for HepC

-Current of former IVDA -Received clotting factor concentrates before 87 or blood transfusions/SOT before 1992 -*Chronic HD* -Known exposure to HCV -*HIV infected* -Children born to HCV+ mothers -*Intranasal drug users* *For all baby boomers, CDC recommends one-time screening regardless of risk factors*

Antiemetics that hit the chemoreceptor trigger zones in the brain stem

-D2 antagonists -NK1 antagonists -CB1 ANTagonists -5-HT3 antagonists

Lefunomide (Arava) clinical pearls

-DDIs: *CYP1A2 substrate and CYP2C9 inhibitor* -Drug elimination procedure with *cholestyramine* for leflunamide toxicity -*CI in pregnancy and breastfeeding*

Ketorolac BBW

-DO NOT use > 5 days due to *GI bleed risk* CI with renal dysfunction, GI bleed, CV disease, cirrhosis Hepatically AND renally eliminated

Hemodynamics in obstructive shock

-Decreased CO -*Increased SVR*

Hemodynamics of cardiogenic shock

-Decreased CO -*Increased SVR* (compensation) -*Increased preload*

Hemodynamics of distributive shock

-Decreased CO (usually) - actually increases at first -Decreased SVR -Decreased preload (less fluid getting back)

Etoposide MOA

-Delays transit of cells through S phase -Topo II inhibitor (ds strand breaks)

Cyclosporine and statins

-Depends on the statin, but some are CI and some you LOWER the dose. It can increase statin levels 2-20 fold -CsA does this by *inhibiting OATP uptake of statins into liver* and inhibiting metabolism FYI ONLY: *Avoid completely* -Lovastatin -Pitivistatin -Simvastatin *Reduce dose substantially* -*Atorvastatin 10 mg Max* -Fluvastatin 40 mg max -Pravastatin 40 mg max -*Rosuvastatin 5 mg max*

Rowasa site of action

-Descending colon -Rectum *Enema - so duh*

Corticosteroids as antiemetics

-Dexamethasone usually used and works in *hypothalamus* -Work by *inhibiting prostaglandin synthesis and elevating mood* *Metabolism* -Majorly metabolized by CYP3A4 and PGP *inhibitor* -Moderate other CYP interactions *Side effects* -Insomnia -Hypertension -Hyperglycemia -Hypotension -Euphoria

Ibrutinib (Imbruvica) side effects - used for refractory GVHD and lymphomas

-Diarrhea -URTIs -Fatigue -Cough -*Neutropenia* -Afib -Hemorrhage

Ibrutinib side effects

-Diarrhea -URTIs -Fatigue -Cough -*Neutropenia* -Afib -Hemorrhage

IBD Preseentation

-Diarrhea -W/orw/o rectal bleeding -Abdominal tenderness and pain -*Weight loss*

Idelalisib (Zydelig) side effects

-Diarrhea -Elevated transaminases -Neutropenia -Anemia, thrombocytopenia *Specific* -Pneumonia! - why? -mTOR resides downstream of p13K and is involved in T cell activation and proligeration, so idela has some *T cell suppression*

Specific indications for PN (starred)

-Diffuse peritonitis -Intestinal obstruction -Inability to gain enteral access -High output (>500 mL/day) proximal fistula -Intractable vomiting -*Paralytic ileus* -Intractable diarrhea -*GI ischemia* -Complications of pancreatitis -Short bowel syndrome -Intolerance or failure of EN

TLS Prevention

-Discontinue contributing meds -Correct pre-existing electrolyte imbalances -HYDRATE -Allopirinol *1-2 days prior to chemo* -Alkalinization of urine with NaBicarb

Entocort (budensonide) site of action

-Distal ileum -Ascending colon Rapid onset

Asacol HD, Apriso, and Liada site of action

-Distal or terminal ileum -Colon These are ORAL, so they get more of the whole tract

Big risk factors for developing CMV infection post-transplant

-Donor positive, especially if recipient negative -Prior treatment with ATG -

High risk features for induction

-Donor specific antibody -African american -*Pancreas > Kidney > Liver*

Xeljanz (tofacitinib) clinical pearls

-Dose reduce in *renal OR hepatic impairment* *DDIs* -CYP3A4 and 2C19 substrate - dose reduce with strong inhibitors Risk of *GI perforation increased with NSAIDs* *AVOID in pregnancy or lactation*

Leflunamide DDIs and drug elimination

-Drug has a 2 week half life and there is an elimination procedure *with cholestyramine* to eliminate by decreasing half life to 1-2 days. Otherwise may take *2 years before undetectable levels* *DDIs* -CYP2C9 INHIBITOR - warfarin concern, statin, etc -CYP1A2 substrate - evaluate smoking status

Genetic tests to be run in ALL *NSCLC patients*

-EGFR -ALK -ROS1 -BRAF -NTRK fusion

EGFR vs KRAS mutation frequency in NSCLC

-EGFR mutations (increased activity type) are often associated with *increased TKI sensitivity* and have *higher freq in NON-smokers, WOMEN*, and non-mucinous tumors -KRAS mutations are associated with increased *TKI RESISTANCE* -Higher KRAS mutation frequence in *Smokers, NON-asian, and mucinous tumors*

IVFE considerations (starred)

-Egg allergy should be evaluated always before initiating - *remember product used, densensitizing is option* -Consider any drugs that contain lipids when calculating lipid PN content

Complications of hyperglycemia in sepsis

-Electrolyte and fluid imbalance -Hyperglycemic hyperosmolar nonketotic coma -*Increased coagulability* - causes more PLT aggregation, coagulation factor activation, fibrinogin, etc. -Increased morbidity and mortality -Increased *susceptibility to infection* -Impaired wound healing -Decreased antibacterial function of PMN

Protective gastric secretions

-Endogenous *prostaglandins* -Mucus -Bicarbonate secretion -Intrinsic epithelial cell defense -Mucosal blood flow

Vasopressin effects in shock

-Endogenous hormone -Potent vasoconstrictor that increases SVR -During hypotension and hypovolemia, vasopressin conc are initially increased and the pressor activity is enhanced -With prolonged shock, concentrations decrease to normal levels in most patients *within 24-48 hours* = "relative vasopressin deficiency"

Hydrocortisone topical forms

-Enema -Foam -Suppository Foam = best tolerated Supp = only rectum

IL-1 functions

-Enhances and prolongs T cell response and antibody production by B cells -IL-1 enables effector T cells to proliferate even in the presence of regulatory T cells -Also increases the *T cell stimulatory ability of dendritic cells*

Which HBV antiviral do you have to take on an EMPTY stomach?

-Entecavir (ETV)

First line agents in HBV *COMPENSATED* cirrhosis per AASLT GL

-Entecavir (LAM -naive) or -Tenofovir (TDF or TAF) *At least 1 year* Longer if HBeAg (-)

First line agents in HBV *DECOMPENSATED* cirrhosis per AASLD GL

-Entecavir (LAM-naive) or -Tenofovir (*TDF ONLY*) MONOTHERAPY RECOMMENDED FIRST LINE At least 1 year Longer if HBeAg (-)

Partially selective NSAIDs

-Etodolac -Nabumetone -Meloxicam -Diclofenac -Celecoxib

Colonoscopy for CRC screening

-Examines entire length of colon -Biopsy and polypectomy may be done during this procedure -Reduced mortality by 60-70% -Every *10 years*

Main use of Precedex in the critically ill patient

-Facilitating extubation -Side effects (hypotension and bradycardia) are main limitation

"Other" additives sometimes in TPN

-Famotidine (2 vials max) -Regular insulin -Carnitine

Disadvantages of fentanyl for pain

-Fat soluble, so can accumulate in tissues with prolonged infusion -Metabolized by *CYP3A4* so must use caution w/hepatic failure -Patient pretty much has to be on a ventilator while on

Opioids that don not cause histamine release

-Fentanyl -Dilaudid

Symptoms of HepB infection

-Fever -Anorexia -N/V -Jaundicen -Dark urine -Clay colored pale stools -Abdominal pain -*Increased AST*

Classifying NSCLC and treatment

-First squamous vs non-squamous - usually is *adenocarcinoma* -Treatment includes chemo, radiation, surgery, targeted therapy, or immunotherapy

Screening tools for colorectal cancer

-Flexible sigmoidoscopy (FSIG) -Colonoscopy (CSPY) -Double contrast barium enema (DCBE) -Computed tomographic colonography (CTC)

CMV infection S/S`

-Flu-like -Fever -Malaise -*Leukopenia* -*Thrombocytopenia* -Diarrhea, vomiting, etc. due to colitis (end organ damage)

Tykerb (lapatinib)

-For HER2/neu+ breast cancer -Appears no cross-resistance with trastuzumab *MOA* -EGFR and HER2 inhibitor *DDIs and side effects* -CYP3A4 substrate -*Cardiotoxicity* -*Hepatotoxicity* Note: studied in combo with capecitabine

Aflibercept (Eylea) MOA

-Fully human fusion protein and decoy *VEGF receptor* Contains VEGFR-1 Ig domain 2 and FEGFR-2 Ig domain 3 attached to human IgG1 Fc *Stronger binding than bevacizumab* *Blocks VEGF and PIGF* - 17 day half life

"Classic" side effects associated with TDF

-GI side effects -Osteopenia -Lipodystrophy

Fam-trastuzumab deruxtecan-nxki (Enhertu)

-HER2 MAb AND *Topo I inhibitor* -For unrestectable or metastatic HER2+ BC after 2 or more anti-HER2 based regimens *Warnings* -*Interstitial lung disease* - unique -Perhaps more *myelosuppression* -Neutropenia -Cardiotoxicity -Fetal toxicity

Ado-trastuzumab emtansine (T-DM1/Kadcyla)

-HER2 targeted Ab PLUS *microtubule inhibitor* -For HER2+ metastatic BC after prior trastuzumab and taxane *ADEs* -Hepatotoxicity -Cardiotoxicity -Infusion rxns -*Peripheral neuropathy* -Fatigue -Nausea -Musculoskeletal pain -*Thrombocytopenia* -HA -Increased LFTs -Constipation

Hypercalcemia of malignancy treatment

-HYDRATION, HYDRATION, HYDRATION -Diuretics once patient is hydrated, do not usually need -*Bisphosphonates - pamidronate and zolendronic acid* -Sometimes Prolia for refractory patients but NOT frontline in this setting

Rate infusion AEs with IVFE (starred)

-Headache -Nausea -Fever During infusion

Sucralfate for PUD pearls

-Helps to heal peptic ulcers, but not widely used *Problems:* -QID dosing -Large tablets -DDIs Counseling: -Do not take *antacid within 30 minutes* -Can alter absorption of some meds so take other drugs *2 hours before taking*

S/S of PUD-induced GI bleed

-Hematemesis (coffee ground emesis or frank blood observed in nasogastric aspirate) -Melena (black, tarry stools) *Signs* -Low Hgb and Hct -If high enough blood loss hypovolemic and patient can be hypotensive and dizzy

Diagnostic/lab tests to order with PUD

-Hematocrit/hemoglobin or stool hemoccult test (if concerns of bleeding or anemia) -BUN/SCr ratio (if concerns with bleeding or dehydration) -H. pylori tests if present with dyspepsia AND worsening or not improving with treatment -Upper endoscopy and/or upper GI radiography with barium is present with dyspepsia (worsening not improving with treatment) OR GI obstruction

Clinically significant ADEs of ribavirin

-Hemolytic *anemia* *CARDIAC DISEASE (CHF, ischemic heart disease, arrhythmias) -Histaminic effects (e.g. cough, sinusitis, itching, pharyngitis) -*Hyperuremia and gout* -*Leukopenia* -Rash *KNOWN TERATOGEN*

Types of hepatitis that can be chronic

-Hep B -Hep C -Hep Delta

S/S of advanced CRC

-Hepatomegaly -Obstruction -*Weight loss* -Jaundice -Leg edema -Thrombophlebitis -Fistula formation -Pain

High dose PPI

-High dose IV continuous infusion PPI for *72 hours* -IV pantoprazole or esomeprazole are basically only options in US -*80 mg IV load then 8 mg/hour IV continuous* Transition to std dose PPI once or twice daily after the 72 hours is complete - if patient cannot tolerate or absorb oral just do intermittent IV bolus as appropriate

Measures to prevent colorectal cancer

-High fiber and low fat diet (NO EVIDENCE) -Aspirin low dose in patients aged *50-69 for at least 10 years if high risk* No other supplement recommendations

Diagnosis of breast cancer

-History and physical exam -*3D mammography can visualize 80-85% of breast cancers* -Other breast imaging techniques like ultrasound

Things that lower risk of chemo induced N/V

-History of alcohol intake -Alcoholics

HYPRESS (2016) study for steroids in septic shock

-Hydrocortisone IV 50 X 1 then infusion *Results* -DID NOT reduce septic shock -DID NOT support using corticosteroids

Cortenema form and site

-Hydrocortisone enema -Rectum and descending colon

Non-major risk factors for SRMB

-Hypotension -Sepsis -Hepatic failure -Acute renal failure -High dose corticosteroids at *> 250 mg/day hydrocortisone or eq* -Multiple trauma -Severe burns (> 35% BSA) -Head injury -Traumatic spinal cord injury -Major surgery -Prolonged ICU admission *> 7 days* -Hx of GI bleeding

The OLD septic shock definition

-Hypotension despite appropriate fluid resuscitation with evidence of *poor perfusion* -CNS -CV -Respiratory -Liver -Renal -Coagulopathy

Chemo regimens for HER2+ patients

-IF patient is axillary lymph node positive, trastuzumab should be incorporated into *adjuvant therapy* -Herceptin can be given with paclitaxel *after AC* or after paclitaxel -Should NOT give herceptin with an anthracycline due to *cardiotoxicity* -*Pertuzumab (HER2 blocker, but diff domain) can be added if patient is at high risk of recurrence* -*Nerlynx (Multi-HER2 TK inhibitor) should be added in EARLY stage after trastuzumab*

Ustekinumab (Stelara)

-IL-12 AND IL-23 Inhibitor *Adverse reactions* -Nasopharyngitis and URTIs -Other opportunistic infections -HA and fatigue -*Induction of crohn's disease* - worsened in some vs placebo -Theoretical risk of specific infections like salmonella

Topo I Inhibitor (irinotecan and topotecan) MOA

-IRREVERSIBLE binding to Topo 1-DNA complex resulting in *single strand (slides say double?) breaks* in DNA -Malignant cells may have higher concentrations of Topo I

Remicade clinical pearls

-IV ONLY -Mild-moderate infusion reactions may occur and infusion should be slowed or interrupted and reinitiated after resolution of reaction. Premed with acetaminophen, antihistamines, and/or corticosteroids *Serum sickness* (delayed hypersensitivity rxn) has been reported and occasionally presents as rash, fever, chills, polyarthralgias, or polyarthritis

Tysabri (natalizumab) clinical pearls

-IV infusion ONLY -Requires enrollment by physician into *TOUCH prescribing program* due to PML risk and facility must be registered -Discontinue therapy for lymphocyte counts *< 500/mm3 AND ANC < 500/mm3* -Dose interruption for *ANC 500-1000 (0.5-1)* and *HgB < 8 or decrease of > 2*

IVFE Considerations (starred)

-IVFE can be used to balance providing adequate calories and minimizing complications IVFE acute AEs RARE: < 1%, but monitor for dyspnea, chest tightness, palpitations, and *chills with 1st dose*

IVFE and hypertriglyceridemia

-IVFE can cause hypertriglyceridemia MUST monitor serum TGs and *decrease if TG > 400* or *HOLD if > 1000 mg/dL*

Bisphosphonates that can be used in HCM with renal dysfunction

-Ibandronate -*Pamidronate* - front line

Antibiotic resistance and PUD treatment selection

-If patient has been previously exposed to any antibiotic, AVOID when choosing PUD treatment regimen -If *clarithromycin resistance in region is > 15%* prefer *BISMUTH quadruple therapy*

Clinical pearls about MTX and NSAIDs

-If using low dose MTX (< 20 mg/wk) can be safe with *non-salicylate NSAIDs and low dose (< 100 mg)* aspirin, PCN, and PPIs

Tacrolimus dose forms

-Immediate release (BID) -Extended release (QD). *Take on empty stomach* NOT INTERCHANGABLE Much more commonly used superior to cyclo in kidney and liver transplant

Remicade indication for RA

-In *combination with MTX* for moderate-severe active disease

HER1/EGFR signalling in colorectal cancer

-In 25-77% of colorectal cancers there is increased HER1/EGFR activvity -Downstream activates genes that cause cell cycle progression -Stimulates *proliferation, angiogenesis, and survival*

Severely malnourished classification definition

-Inadequate dietary intake for *> 1 month* and/or anorexia hx -Vomiting or diarrhea *> 2 weeks* -Visual somatic protein wasting -Loss of *>10% UBW in last 6 months or loss of >5% UBW in last 1 month*

Moderately malnourished or suspected malnourishment classification definition

-Inadequate dietary intake or hx of anorexia -Vomiting or diarrhea *> 2 weeks* -Weight loss *between 5-10% in last 6 months*

Breast cancer epidemiology

-Incidence AND mortality increases with increasing age -Median age at Dx is 62 -*Caucasian > African American > all other races* -Men only 1% incidence and mortality

Amlodipine, nifedipine, and phenytoin interaction with CsA

-Increase risk of gingival hyperplasia

Outcomes from coordinating SATs and SBTs

-Increased # of vent free days -Decreased ICU and hospital LOS -Shorter duration of coma

JAKi lipid efffects

-Increased total cholesterol, LDL, and HDL -Interestingly, active RA is associated with reduction in LDL and TC -Usually see effect in *4-6 weeks after starting* Unclear significance, consider getting lipids *8 weeks after initiation and as usual*

Fecal Occult Blood Testing (FOBT)

-Increases diagnosis in *early stage* -Misses small adenomatous polyps -*60% false positives* -20-25% false negative *Reasons for false positives* -Red meat, blood sausage -Vegetables with peroxidase activity -Iron -Gastric irritation (NSAIDS) *False Negatives* -Vitamin C

Hepatic artery drug infusion

-Increases drug exposure in the liver -*FUDR (floxuridine)* 0.3 mg/kg/d admin as continuous 24 hr infusion X 14 days provides *higher response rates compared to IV*. Use heparin to decrease arterial thromboses and dexamethasone to limit hepatobiliary toxicity

Big problem with morphine use in ICU patients

-Induces histamine release, so can lead to *hypotension* -Accumulation of active metabolite morphine-6-glucuronide in liver or renal dysfunction

Morphine disadvantages for pain control

-Induces release of histamine and can lead to *hypotension* - *AVOID in shock* -Active metabolite morphine-6-glucuronide can *accumulate in hepatic and renal dysfunction*

Tolfacitinib adverse effects

-Infection -Dyslipidemia -Headach

Tolfacitinib adverse effects

-Infection -Dyslipidemia -Headache

Baricitinib (Olumiant) side effects

-Infection -Dyslipidemia -Transaminitis

Orencia (abatacept) adverse effects

-Infection -HA -HTN -Hypersensitivity (possible anaphylaxis)

Rituxumab side effects

-Infusion related reactions -Infection *Note: May infuse IGs to prevent viral infection because they are no longer produced* *BBW for Hep B virus reactivation*

NS3/4 inhibitor (previrs) MOA

-Inhibit the viral *protease* -Bind to catalytic site of protease and *block post-translational processing* of viral polyprotein resulting in prevention of release of function NS proteins

Idelalisib (Zydelig)

-Inhibitor of *P13K-delta* -Inhibits proliferation and induces apoptosis in B cells -Inhibits the homing and retention of malignant B cells in lymphoid tissue reducing survival

Pemetrexed mechanism

-Inhibits *thymidylate synthase, DHFR, glycinamide ribonucleotibe, snf formyltransferase (GARFT) -All are *folate-dependent enzymes* involved with nucleotide synthesis -Pemetrexed is *converted in the cell via polyglutamylation*

Cyclosporine DDI with everolimus and sirolimus

-Inhibits CYP3A4 and PGP -*Increases SRL and ERL* levels if used with CsA Do not confuse with mycophenolate, CsA decreases MPA levels - so you need HIGHER dose

Hydroxychloroquine mechanism

-Inhibits intracellular *toll-like receptors* and *decreases TNF production* and interferes with TNF release

When to start and adult TPN

-Initiate based on nutrition assessment and inability of patient to meet nutritional needs orally or enterally for a period of time *TPN is not an emergent or fast intervention* - takes TIME to work

Actemra (tocilizumab) adverse effects

-Injection site reactions -Infusion reaction (IV) -Transaminitis -Infection -HTN -Dyslipidemia -*Neutropenia and thrombocytopenia*

Desired PK of pain med for *intermittent dosing*

-Intermediate half life

Nonpharmacologic RA tx recommendations

-Joint protection education (eh on evidence) -*Physical exercise* and sports -*INSOLES can make huge difference* *Ineffective or Dangerous* -Dietary changes and especially elimination diets

Which HCV drug is not safe in all stages of renal dysfunction and HD?

-Just ribavirin (RBV)

PN adjustments in renal dysfunction

-K, Mg, and phos may increase, so lower levels in TPN accordingly -Protein needs are lower (*0.8-1 g/kg for non-HD renal deficiency*) If on HD, make sure to get electrolyte levels BEFORE HD

KRAS gene and the EGFR pathway (Colon cancer)

-KRAS gene may be normal (WT) or mutated -Wild-type KRAS is active for a short period when the EGFR is stimulated. Very tight control. -When *KRAS is mutated, protein is permanently on* even without EGFR signalling, so inhibiting EGFR with cetuximab probably won't do as much *KRAS falls downstream of EGFR path and leads to increased gene transcription and cell cycle progression*

2018 PADIS Guidelines and new drugs added

-Ketamine AND nefopam have been added to guidelines and are recommended as *adjunct analgesics to opioids*

Belatacept qualifications to use

-Kidney transplant ONLY -Must be *EBV seropositive*, CI if negative or unknown

IVFE (IV fat emulsion) basics

-Know the source of lipids to ensure no allergies *Soyban oil in most* - 10%, 20%, 30% IV soybean and olive oil now available in 20% ONLY Both types contain *egg phospholipids* (emulsifying) and glycerol (make isotonic)

Which drugs (based on genotype) are recommended for *decompensated cirrhosis*?

-LDV/SOF (Harvoni) -VEL/SOF (Epclusa) -SOF (but not alone?) *MUST ADD low dose Ribavirin (600 mg QD) to these regimens and renally adjust if needed*

HBV drugs approved for compensated AND decompensated cirrhosis

-Lamivudine -Entecavir -Tekbivudine -Tenofovir disproxil fumarate

Nucleoside analogs for HBV

-Lamivudine -Entecavir (guanosine analog) -Telbivudine (HBV specific) LET side

Lung cancer epidemiology

-Leading cause of cancer death in men AND women -Super poor prognosis with 5 year survival rate of 19.4%

ATG side effects

-Leukomenia, thrombocytopenia -Cytokine release storm -*Pulmonary edema* -Serum sickness -Increased risk of infection

ATG side effects

-Leukopenia -Thrombocytopenia -Cytokine release syndrome (fever, chills, myalgia, HTN, N/V/D) -*Pulmonary edema* -*Serum sickness* -Increased risk of infection

Valganciclovir adverse effects

-Leukopenia -Thrombocytopenia -GI ALL things that can be caused by CMV infection

mTOR inhibitor ADEs

-Leukopenia, anemia, and thrombocytopenia -*Hypercholesterolemia* -*Peripheral edema* -Impaired wound healing and dehiscense -*Mouth ulcers*

Mycophenolate side effects

-Leukopenia, anemia, and thrombocytopenia -*Diarrhea* -Abdominal pain -Nausea and vomiting *REMS program - causes congenital malformation and 1st trimester pregnancy loss - use BUM too due to DDIs*

Adverse effects of pemetrexed

-Leukopenia, thrombocytopenia, anemia -Mucositis -Rash, desquamation, itching -Constipation OR diarrhea -Peripheral neuropathy -LFT elevation, nephrotoxicity - *Avoid NSAIDs* as they can decrease CL by 20% -Pneumonitis -Arthralgia -Mild nausea

Substance P/NK1 receptor antagonist mechanism

-Little to no affinity for serotonin, dopamine, and corticosteroid receptors but affects chemoreceptor trigger zone *FDA Approval* - only in combination with dexamethasone and serotonin antagonists

Common sites of breast cancer metastasis

-Liver -Lung -Bone -Brain -Lymph nodes

Dopamine receptors

-Located in *renal, splanchnic, coronary, and cerebral vascular beds* -Effect depends on dose

Vasopressin receptor stimulation

-Located in vascular smooth muscle -*Constricts vascular smooth muscle and increases responsiveness* to catecholamines - overall *increases sympathetic nervous system activity*

Risk factors for liver disease from TPN use (PNALD)

-Long duration of PN -Long term administration of excess calories (overfeeiding)

Maintenance phase of immunosuppression

-Long term immunosuppression required for the life of the graft -Intensity can often be tapered over time and involves multiple agents

Potassium requirements in TPN

-Look at what pt is receiving peripherally -*NEVER double K in TPN* - if you need aggressive supplement it is safer outside of TPN

Flexible sigmoidoscopy

-Looks at lower half of colon -Longer size allows visualization to splenic flexture -*60-70% mortality decrease* (after agee 50) -Do every 5 years + gFOBT every 3 years

Double contrast barium enema

-Looks at the entire length of the colon, but some small polyps may be missed

Ziprazidone and aripirprazole benefits in delirium

-Low and very low sedation -Low EPS -Very low NMS incidence (aripiprazole) -Low weight gain *Note: Ziprasidone has moderat QTc prolonging*

Pentasa site of action

-Lower small intestine -Colon This is the only one that is ORAL but has different site - why? Beccause it is a *coated capsule*

Adverse effects of valganciclovir

-Luekopenia -Thrombocytopenia -*GI effects*

LCTs vs MCTs in IVFEs

-MCTs could provide some advantage in *critically ill patients* *Advantage of MCTs* -Cleared more rapidly and hydrolyzed -No liver accumulation -Do not require carnitine for entrance into mitochondria for oxidation *MCT disadvantages* -Not a source of essential FAs

Conventional DMARDs

-MTX -Hydroxychloroquine (HCQ) -Sulfasalazine (SUL) -Leflunomide (LEF)

DMARDs that are category X

-MTX -Leflunamide

Nutrition Assessment (Starred)

-MUST be completed prior to starting EN or PN *Primary Goal:* - ID, prevent and correct malnutrition before it becomes a factor leading to patient morbidity and mortality *Includes subjective and objective data* -Med and surgical hx -Diet history -Anthropometic measurements -Biochemical assessment -Physical eval

Important Med and Surgical History to collect from patients

-MUST know the *GI sites affected* AND *where specific nutrients are absorbed GI resected patients for example may be at risk for malabsorption and nutritional deficiencies

MYC and DLBCL

-MYC is normally a *transcription regulator* (known oncoprotein) and is overexpressed in some DLBCLs -Abnormalities (overexpression) cause aberrant and aggressive DNA transcription and *cell proliferation* MYC positive DLBCL has pretty poor outcomes

Secondary goals for Crohn's Disease

-Maintain steroid free remission -Resolving fistulizing disease -Decrease complications and surgery -Preserve intestinal function -Improve patient QOL -Minimizing adverse effects of therapy

Which trace elements undergo biliary elimination, thus must be removed with cholestasis?

-Manganese -Copper Risk manganese induced neurotoxicity Copper removal is dependent

What do we give with cisplatin to help prevent nephrotoxicity and electrolyte deficiencies?

-Mannitol to prevent nephrotoxicity -Magnesium and potassium provided with infusion

JAK/STAT Pathway

-Many of the ILs and IFN-y utilize the JAK/STAT pathway and are required for *dimerization of JAK 1, 2 or 3* -Dimerization allows *phosphorylation of STAT* and thus *increased T cell proliferation*

H2RA DDIs

-May alter BA of oral drugs -Cimetidine in particular inhibits several CYPs with many DDIs -Famotidine is all good

Actemra (tocilizumab) clinical pearls

-May develop *neutralizing antibodies against med* -INDUCES *multiple CYPS* -Possibly unsafe in *pregnancy*

Orencia (abatacept) clinical pearls

-May develop *neutralizing antibodies* against med -*DO NOT RUB injection site*

Kevzara (sarilumab) clinical pearls

-Me too drug of tocilizumab -Hold if *ANC < 2, PLT < 150, or AST/ALT > 1.5 ULN* -Possibly unsafe in pregnancy

Activated B Cell-like (ABC) DLBCL

-Median age is 66 years (older than GCB) -Cells are ABLE to differentiate into *plasma cells* however B-cell surface receptors become *overstimulated* leading to constant stimulation of *Nuclear Factor kB (NF-kB)* and potential *overexpression of MYC or BCL2* (remember venetoclax inhibits) -Thus it is caused by *EXPRESSIONAL change* rather than a DNA mutation like GCB during development Survival is much lower with 5-year median of 30%

Germinal Center B Cell-like (GCB) DLBCL

-Median age of Dx is 50 years (younger) -The GCB cells do NOT differentiate appropriately - thought to arise from NORMAL germinal center B cells -During maturation process, mutations occur and *mutated DNA leads to mutated cells - thus caused by a GENETIC MUTATION during differentiation* -5 year survival is 59% Note: You DO NOT find NF-kB pathway in GCB, ONLY ABC

Th17 Cells

-Memory T cells that reside in the bone after promotion by *IL-23* -Produce *IL-17 and IL-22* - IL-17 more important

IL-5 inhibitor to know (hint for eosinophillic asthma)

-Mepolizumab -Binds to *free IL-5* NOT the receptor (but we do have a drug for that)

Signs of PRIS

-Metabolic acidosis -Rhabdo -Acute renal failure -CV collapse -*Hyperkalemia*

Etoposide special metabolism /dosing considerations

-Metabolism is hepatic, but in hepatic compromised states, the kidneys *compensate via renal clearance* -ONLY consider dose adjusting with BOTH hepatic and renal dysfunction -Etoposide phosphate is the drug, but order by how much *Etoposide parent drug desired* *CYP3A4 substrate*

Precedex pearls

-Metabolized by *CYP2A6* in liver -Monitor for *hypotension and bradycardia* (greater incidence than propofol) -Potential withdrawal hypertension *CONTRAINDICATED in patients with seizure disorder*

Hydromorphone good points over fentanyl

-Metabolized via glucuronidation, so useful in *renal insufficiency* -Uncommon to give continuous

ATG premedication meds

-Methylprednisolone -Acetaminophen -Diphenhydramine Must infuse over 4-6h through and *in-line filter*

FLT3 Inhibitors

-Midostaurin -Gilteritinib -Sorafenib If sorafenib sounds familiar it is because we learned it in medchem w/regorafenib it is VEGF inhibitor (stops angiogenesis) along with all the other agents in this class to some extent. These all are actually *multi-kinase inhibitors*

Hand-foot syndrome

-Moderate pain and redness of the mouth, swelling of the mouth, or mouth sores -Moderate pain, swelling, and redness of hands or feet *Use tons of moisturizer*

Cimzia (certolizumab pegol) indications in RA

-Moderate to severe active disease *with or without DMARDs*

Humira indication in RA

-Moderate-severe active disease *with or without DMARDs*

Propofol monitoring need

-Monitor serum triglycerides *every 3-7 days* -Consider alternative if serum *TG > 400*

Innate immunity cells

-Monocytes -Macrophages -Neutrophils -Eosinophils -Basophils -Mast cells -Natural killer cells

Which org reccommends breast self exams

-Monthly if > 20 years -Remember there is no evidence this is just best practice

IgG Antibody

-Most abundant (70-75%) Ab in blood AND tissue -Main component of *secondary response* (MEMORY) -Coats microorganisms and activates complement system -Crosses placenta to provide *passive immunity*

Principles of lung cancer chemotherapy

-Most efficacious in rapidly dividing cells -Generally cytotoxic and non-specific (effects normal cells too) *Timing in lung cancer* -Used concurrently with radiation -Used when patient not a candidate for radiation and/or surgery -Used when patient's tumor progresses -Backbone of treatment in SCLC *How do you choose medication?* - Extent of disease (efficacy in that stage) -Toxicity profile

Acute vs Chronic HBV

-Most people will only develop acute infection which can be asymptomatic to mild or rarely fulminant hepatitis. Severe in *>60 yo* *6-10% of older children and adults will develop chronic disease*

Propofol vs Dexmedetomidine in the SPICE III Trial

-Much higher incidence of hypotension and bradycardia with dex (2.7% and 5.1% vs < 1%) -More side effects with dex in general -Subanalysis showed possibly *decreased mortality with dex in younger patients and decreased with propofol in older* Note how low the actual rate of these side effects s

The CPOT assessment includes what that BPS does not

-Muscle tension -Vocalization *Higher score does NOT mean more pain necessarily* though

TPN monitoring needs due to dextrosee

-Must *monitor blood glucose* and adjust based on glucose measurements -Can consider adding insulin in setting of hyperglycemia and patients with diabetes or pancreatic insufficiency

Ribavirin Clinical Pearls

-Must dose adjust for anemia (*Hgb < 12 w/cardiac disease < 10 w/o) *Contraindications* -Women who are pregnant -Men whose female partner is pregnant -Breastfeeding -Patients with hemoglobinopathies *Preg Category X* -Need BC for patient and opp sex partner -Recommend *two forms of contraception* regardless of who is receiving treatment during treatment and *6 months after RBV is discontinued*

Mavyret (glecaprevir and pibrentasvir) clinical pearls

-Must take *with food* -CONTRAINDICATED with *coadmin of atazanavir and rifampin* -Use *Contraindicated in Child-Pugh B and C* -No dose adjustment necessary for renal impairment

Fludarabine side effects

-Myelosuppression -*Autoimmune hemolytic anemia/thrombocytopenia* -*Idiopathic thrombocytopenia purpura*

Carboplatin toxicities

-Myelosuppression with nadir (initial phase) being 21 days and recovery 28 days. *Thrombocytopenia is the DOSE LIMITING side effect* -Mucositis -Rash, hyperpigmentation -Hypocalcemia, hypokalemia, hyponatremia, hypomagnesemia -N/V/Diarrhea -Transient increase in LFTs -Nephrotoxicity (less than cisplatin)

Cisplatin adverse effects

-Myelosuppression: Nadir (lowest) in first 14-23 days, recovery after 21-39 days -*Nausea and vomiting* -*Nephrotoxicity* -Peripheral neuropathy -*Ototoxicity* -Increase in LFTs Electrolyte problems -*Hypomagnesemia* -*Hypokalemia* -Hypocalcemia -Hyponatremia -Hypophosphatemia

Adverse effects of taxanes

-Myelosuppression: Nadir 11 days, recovery 15-21 days -Flushing -Abnormal EKG -Alopecia (bald monkey) -*Hypersensitivity w/ paclitaxel* (taxol form) -N/V/diarrhea -*Peripheral neuropathy* -Arthralgias, myalgias, fatigue -Increased LFTs -*Visual disturbances w/Abraxane (albumin bound paclitaxel)*

Etoposide adverse effects

-Myelosuppression: Nadir 7-14 days and recovery 21-28 days -Nausea, vomiting, mucositis -Alopecia -Ovarian failure, amenorrhea

Adverse effects of topo I inhibitors (e.g. irinotecan)

-Myelosuppression: Nadir is 21-29 days and recovery 27-34 -*Diarrhea - can be SEVERE and life threatening* - early w/in 24H do atropine and late do loperamide -N/V -Mucositis, cramps,constipation -Cholinergic toxicity: rhinitis, diaphoresis, flushing -Fever, dizziness, insomnia

Rituximab for RA adverse effects

-N/V -UTI -Infection -*Neutropenia* -Infusion reactions -Pruritis -*Thrombocytopenia* -*Hypophosphatemia*

Breakthrough N/V

-N/V occurs despite treatment with antiemetics -Need more

Ductal carcinoma in situ (DCIS)

-NON-invasive -*Premalignant* lesion -Usually curable with resection alone

Refractory nausea and vomiting

-NOT manageable with current antiemetics -Have to use an agent from a different class

Lobular carcinoma in situ (LCIS)

-NOT premalignant and *NON-invasive* -However is a risk factor for breast cancer

-Buvir class

-NS5*B* polymerase inhibitor

Lowest efficacy, but least resistant DAA class

-NS5B *non-nucleoside inhibitors*

Major tacrolimus toxicities

-Nephrotoxicity -Neurotox (tremor, HA) -*Hyperglycemia (new onset DM)* -*Alopecia - hair LOSS* -*DIARRHEA*

Major cyclosporinee toxicities

-Nephrotoxicity -Neurotoxicity (tremor, HA) -*Hyperlipidemia* -*Hyperuricemia* -*Hirsutism - hair growth* -*Gingival hyperplasia*

Ribavirin clinical pearls

-Never use as monotherapy - added therapy to HCV regimen

Nitrogen impact on TPNs

-Nitrogen is a *protein substrate* and is a byproduct of protein metabolism -We want to *decrease N excretion* In patients with normal renal function *80% of N is excreted in urine*

Epinephrine PD

-Nonspecific *alpha and B-adrenergic agonist* *CO increased at LOWER doses and vasoconstriction dominates at higher doses* Added on to NE in septic shock but usually reserved for failing - impairs blood flow to splanchnic system, increases lactate level, and causes dysrhythmia more frequently than NE

BCL2 and DLBCL

-Normally sequesters BIM and BAX, which are proteins responsible for triggering *mitochondria-induced apoptosis* - apoptosis is a NORMAL process in these cells and should happen. -Aberrant and aggressive expression of BCL2 prevents cell apoptosis. Basically sequesters all the BIM and BAX so it cannot translocate to the *mitochondria and induce apoptosis*. They essentially stimulate *Cytochrome C release from mitochondria* which activates caspase-9 and induces apoptosis

Haloperidol for delirium

-Not great but often used -onset in 30-60 min *ADEs* -QT prolonging -EPS -Anticholinergic

Disease state and lifestyle risk factors for colorectal cancer

-Obesity -Alcohol -Tobacco -Occupational exposures (asbestos, pesticides, herbicides) -Diabetes (metformin in women may decrease risk) -*Vitamin D deficiency* - those more likely to be deficient but role of supplementation and or screening to prevent is unclear

Treatment of LCIS

-Observation could add tamoxifen OR -Bilateral mastectomy with or without reconstruction

HMA based regimen place in AML therapy

-Often used in *older patients* who have a high ECOG score - they are deemed as not able to tolerate intensive chemotherapy like FLAG or 7+3

Sovaldi (sofosbuvir) clinical pearls

-Ok in ALL stages of renal impairment and HD -Rifampin and SJW should NOT be used because they can significantly decrease SOF plasma concentrations -Serious life threatening cases of *symptomatic bradycardia* (1 case fatal cardiac arrest) in patients who received Harvoni or SOF + another DAA in *combination with amiodarone*. AVOID combination

Treatment and prevention of HAV

-Only pre or post exposure prophylaxis in persons who cannot be vaccinated: *< 12 months, > 40 years of age, CLD, allergic* *Treatment option* -Immunoglobulin provides passive immunity (*<3 to 5 months*) and more effective if given during *1st 2 weeks of infection*. Available IV and IM.

Gabapentinoid limitations for pain

-Only useful for neuropathic pain -*Renally eliminated* so must dose reduce or stop in renal dysfunction

Talazoparib (Talzenna)

-PARP inhibitor -Pgp substrate *Common ADEs* -Fatigue -HA -Alopecia -Hyperglycemia -Nausea -Diarrhea -Myelosuppression -Increased LFTs

Olaparib (Lynparza)

-PARP inhibitor only for HER2- BRCA1/2+ -DDI: 3A4 substrate *Common ADEs* -Edema -HA -Rash -Nausea -Diarrhea -Myelosuppression -Fatigue

Rituximab +/- Idelalisib for CLL. What is best?

-PFS increased substantially in the idelalisib PLUS rituximab group Adding P12K-delta inhibitor obviously does something more

Bismuth quadruple therapy regimen

-PPI (standard dose) PLUS 1. Bismuth subcitrate (120-300 mg) or subsalicylate (300 mg) *QID* 2. Tetracycline 500 mg *QID* 3. Metronidazole 250 mg BID 10-14 day regimen

Causes and mechanisms of hypercalcemia of malignancy

-PTH related peptide (released from cancerous squamous cells - lung, esophagus, cervix) -PTH hormone oversecretion -Vitamin D overproduction -Direct osteolytic effects of tumor on bone

Taxanes MOA (ones used in lung cancer?)

-Paclitaxel and docetaxel used -Both *promote assembly of and STABILIZE microtubules* by binding to the *beta subunit of tubulin* (tubulin = monomer building blocks of microtubules) -Inhibit mitosis by inhibiting reorganization required by microtubules -Also binds to apoptosis stopping protein called *BCL2 (yes, the one Venclexta inhibits) arresting function* Note: Opposite vinca alkaloids which promote DISassembly

Hypercalcemia of malignancy presentation

-Patients are more symptomatic with fast changes -Ionized calcium best indication but also do serum Ca *Symptoms* -Constipation -Lethargy -Abdominal pain -Polyuria -*EKG changes* - shortened QT interval -Acute renal failure, seizure coma, death

Chronic HCV infection warning signs

-Patients can be asymptomatic for years -RARE extrahepatic manifestations - most common *cryoglobulinemia; +ANA* -Most have *necroinflammatory disease on liver biopsy and/or fibrosis*

Methadone major uses

-Patients previously on methadone -Pediatrics

IVFE contraindication (starred)

-Patients with impaired clearance of fat emulsion (e.g. pathologic hyperlipidemia, hypertriglyceridemia associated with pancreatitis)

Radiographic findings in RA

-Periarticular osteoporosis -Joint space *narrowing* -Bone *erosions*

Serotonin antagonists mechanism and side effects

-Peripheral (GIT) AND central 5-HT3 antagonism KNOW: -*HEADACHE* -*Constipation* -*QT prolongation* (exception palonosetron) -Lightheadedness -Dry mouth EPS

Fat types of IVFE

-Polyunsaturated long chain triglycerides (TGs) (linoleic acids) -Unsaturated LCTs (oleic acid) -Saturated LCTs (palmitic and stearic acids)

Triple negative breast cancer

-Poorest prgnosis -Must be PD-L1 > 1% to use immunotherapy *Treatment* 1. Atezolizumab + nab-paclitaxel (Abraxane) 2. Pembrolizumab + eribulin (NOT FDA approved YET)

Norepinephrine PD

-Potent alpha agonist (increases MAP and SVR) -Less pronounced B-agonist effect. Cardiac output is *unchanged or slightly increased* -*More potent than dopamine* in refractory septic shock

MTX Contraindications

-Pregnancy (Cat X) -Breastfeeding generally CI - withhold for *>24 hours after dose* -Alcohol use disorder -Chronic liver disease -Immunodeficiency (e.g. transplant and HIV) *CAUTIONS* -Use in older age (> 65) -Renal dysfunction (no strict numbers for cutoff)

Epidemiology of RA

-Prevalence is 1% and increases with age -No racial bias -*Females 3-6X more likely to get than males* -Environment and genetics hve a role

Polyps and colorectal cancer

-Primarily adenomatous -Polyps decreased in *FAP with COX2 inhibitors*

Capecitabine (Xeloda) MOA and side effects

-Pro-drug of 5-FU that has similar ADEs to protracted infusion regimens of 5-FU -*Diarrhea* -*Stomatitis* -N/V -Minimal myelosuppression -*Hand-foot syndrome* -Alopecia

Mycophenolate mechanism

-Pro-drugs of mycophenolic acid (MPA) MPA inhibits *inosine monophosphonade dehydrogenase (IMPDH) and de novo guanine nucleotide synthesis* MPA selectively inhibits lymphocyte proliferation *Note: enterocytes also use de novo guanine nucleotide synthesis, so inhibiting leads to DIARRHEA*

Sulfasalazine in pregnancy and lactation

-Probably *SAFEST* in pregnancy -Mixed data in lactation, there is a concern for *G6PD deficciency* and it is not routinely screened

Hydroxychloroquine clinical pearls

-Probably *least bone marrow suppression* of any DMARD -*SAFE in pregnancy* and compatible with breastfeeding -Both *exacerbates AND treats *treats porphyria* -*Exacerbates psoriasis* -Doses higher than *600 mg* significantly increase risk of *retinopathy* Takes *weeks to months for full effect*

Mycophenolate MOA

-Prodrug of mycophenolic acid (MA) -Inhibits *IMPDH* and thus *de novo guanine synthesis* to selectively inhibit lymphocyte proliferation

Etoposide metabolism

-Protein binding is high at 94-98% -Metabolism mainly hepatic by *CYP3A4, 3A5, and UGT1A1 substrate*

LT problems with chronic steroid use after transplant

-Psychosis -Cataracts and glaucoma (vision change) -Hypertension -Glucose intolerance -Osteoporosis

Oxaliplatin MOA and side effects

-Pt drug: DNA crosslinker to inhibit DNA synthesis and denature *Dose limiting = peripheral neuropahty* -*COLD induced neuropathy* -Lacks nephrotoxicity (not like cisplatin) -Limited hematologic toxicity -Liver toxicity -GI toxicity - N/V and diarrhea

RA cycle during pregnancy

-RA tends to *improve in pregnancy and often spontaneously remit* -Flares are common in the post-partum setting

Classifying SCLC

-Rapidly growing cells and early metastatic disease -Treatment includes chemo, radiation, surgery (only if single node), and immunotherapy but *NOT targeted therapy*

TNFi classic adverse effects

-Rash -URTIs -Nasopharyngitis -Headache

Panitumumab (Vectibix) + side effects

-Recombinant IgG2 kappa MAb that *binds to EGFR* -Similar to cetuximab *Acneform rash (VERY COMMON)* For treatment of EGFR-expressing, metastatic CRC with disease progression following 5-FU, oxaliplatin, and irinotecan containing regimens *Same KRAS issue as cetuximab - need wild type*

Stress ulcer prophylaxis recommendation in septic shock

-Recommended in patients with *sepsis or septic shock who have risk factors for GI bleeding* *Risk Factors* -Mechanical ventilation > 48 hours, coagulopathy Use either PPI or H2RA - *H2RA first line* *Hypotheses* -Disrupted protection against gastric acid -Gastric mucosal hypoperfusion -Increased acid production -Oxidative GIT injury

Topical hydrocortisone side effects in IBD

-Rectal pain -Irritation -Rectal injury *Fewer SEs than systemic*

Secondary goals for ulcerative colitis

-Reducing need for long term steroids -Improved patient QOL -Decreasing risk of cancer

HAV Life Cycle

-Releases into blood and *secreted into bile, then reabsorbed or excreted in stool* -Liver damage results from immune mediated injury with cytolytic T-cells (NOT cytopathic). This *increases LFTs* -Clinical symptoms appear at onset of immune response

Hydroxychloroquine precautions

-Renal and hepatic impairment (no dose adjusting, but monitor) -GI disorders (can cause GI distress) -*Exacerbation of psoriasis* + small SJS risk -*Porphyria - exacerbates AND treats*

Nonpharm treatment of delirium in the ICU

-Repeated orientation of patient -Cognitively stimulating activities -Normalization of *sleep/wake cycles* -Early mobilization and range of motion activities -Timely removal of catheters and physical restraints -Use of eyeglasses and hearing aids -*Early correction of dehydration*

Nonpharm strategies for delirium

-Repeated reorientation -Cognitively stimulating activities -Normalize *sleep/wake cycles* -Early mobilization -Timely *removal of catheters and restraints* -Use *eyeglasses and hearing aids* -Early *correction of dehydration*

IgA antibody

-Represent *15-20% of Ig pool* -Found in body secretions and mucous membranes -Guards the bodies entrances - a *barrier Ab* -Prevents attackers from *sticking*

Rituximab clinical pearls

-Requires premed with tylenol, methylpred 100 mg IV, and antihistamine -*PML risk* (not recommended routine testing) -Can develop *neutralizing antibodies against* -*CV reactions* -Manufacturer advises *against use in pregnancy and lactation* - contraception *X 1 year from last dose and delay lactation for 6 months from last dose*

IgE antibody

-Responsible for bad effects with allergic reactions -Smallest quantity of all Ig -*Sensitizes cells on mucosal surfaces* (eyes, nose, lungs) -Triggers basophils to release histamine

EGFR TKI mechanism of action

-Reversibly inhibit kinase activity of wild-type and certain mutations of EGFR -*Prevents autophosphorylation* of tyrosine residues associated with receptor, inhibiting further down signalling and blocking EGFR dependent proliferation

Extra-articular manifestations of RA

-Rheumatoid *nodules* (20%) -*Splinter hemorrhages* -*Lung damage*(tobacco worsens!) resulting in pulmonary fibrosis -Anemia

Black box warning for all direct acting antivirals

-Risk of activation or reactivation of HepB viral infection. Health care professionals should screen all patients for evidence of current or prior HBV infection before starting treatment with DAAs, and monitor patients using blood tests for HBV flare-ups or reactivation during treatment and post-treatment follow up

Humira clinical pearls

-Rotate injection site

H. pylori-induced GI bleed treatment

-SAME as for H. pylori PUD (clarithromycin triple or bismuth quadruple) -Follow GI bleed initial treatment approach - active bleed to IV PPI -Post treatment testing recommended AFTER treatment of H. pylori can *STOP PPI or H2RA* if cure is documented

Small cell lung cancer (SCLC) treatment differences from NSCLC

-SCLC is a highly disseminated (spread out) disease in most patients at presentation and is *very responsive to chemotherapy* thus chemo is a major component of treatment -Surgery is rarely used -Most patients with LIMITED disease will receive radiation + chemotherapy because addition of radiation has been shown to prolong survival -They actually use prophylactic brain irradiation in a lot of cases to prevent brain metastasis and prolong survival For extensive stage use chemo +/- immunotherapy first maybe radiation later if complete or partial response

Treatment monitoring and endpoints

-SVR 12 and 24 (*most studies using 12 now due to high sensitivity and selectivity*) -*Q80K polymorphism (may be associated with lower SVR rates)

Vosevi (sofosbuvir, velpatasvir, and voxilaprevir) clinical pearls

-Same CIs as SOF/VEL (Epclusa) *Voxilaprevir specific* -Not recommended and AVOID in *Child-pugh B or C* due to higher exposure of voxila -NOT recommended to be coadministered with *PGP inducers and/or moderate to potent CYP inducers* -Same acid reducing agent problems/recs as SOF/VEL, BUT *omeprazole 20 mg can be used with VOSEVI - NOT other PPIs* -Ok in all stages of renal impairment and HD

Sarilumab (Kevzara)

-Same as tocilizumab practically -Probably unsafe in pregnancy too

2018 PADIS Pain Management Guidelines

-Say that opiates remain "mainstay" for most ICU settings (removed first line) -Now more focus on adjuvants to opioid therapy *Key Points* -Continuous infusion or intermittent scheduled dosing provides improved analgesia -Assess pain pre AND post intervention -Parenteral preferred in critically ill patients - transition to oral once tolerated

ACS Screening recommendation for patients with personal h/o curative intent resection of CRC

-Screen within 1 year after resection regardless of age -*Colonoscopy in 3 years then every 5 years*

Chief cell function

-Secrete *pepsinogen* -Pepsin is activated in lower (acidic) pH and inactivated at higher pH. -Pepsin (cofactor) also takes part in the *proteolytic activity involved in ulcer formation*

Parietal cell function

-Secrete gastric *acid* -Contain *histamine, gastrin, and ACh receptors* - binding to these receptors stimulates acid secretion into stomach

Trastuzumab (Herceptin)

-Selectively binds to HER2 -4 mg/kg IV loading dose then 2 mg/kg weekly -Risk of *cardiotoxicity* increased with anthracyclines or taxanes

What should you add to TPN if experiencing excess GI losses?

-Selenium -Zinc

How does HBV spread?

-Sexually, parenterally, and perinatally *Most common* -Sexual activity -IVDA *HBV is 50-100X more infectious than HIV*

Acute vs. chronic electrolyte abnormalities and TPN

-Should *correct acute with dose* -TPN should be used for chronic abnormalities only Adjust electrolytes based on *serum levels and clinical status*

Belatacept in kidney transplant outcomes

-Similar graft and patient survival to CsA based regimen -Higher rejection rate, but *better eGFR long term than CsA based* No data in non-renal

Pertuzumab (Perjeta)

-Similar to herceptin, but targets *subdomain of HER2* and inhibits via 2 major paths: *MAP and PI3K* *Uses* -Metastatic BC w/ herceptin and docetaxel -Neoadjuvvant in high risk -Adjuvant in high risk *ADEs* -Cardiotoxicity (LV dysfunction) -Diarrhea

Maintenance chemo for NSCLC

-Similar to other regimens. Initial *induction with higher doses and multiple drugs* *Continuation maintenance*: Use of at least 1 agent given in first line *beyond 4-6 cycles* in ABSENCE of disease progression *Switch maintenance*: Use of agent *NOT used in first line* -Initiate pemetrexed after Pt doublet chemo in nonsquamous without specific mutations -Initiate docetaxel after Pt doublet chemo to

Small cell lung cancer (SCLC). What do these cells not express that NSCLC does?

-Small cells with *round nuclei* -15% of all lung cancers -*Highly AGGRESSIVE* -*DO NOT express EGFR or ALK*

Regorafenib (Stivarga)

-Small molecule multi-tyrosine kinase inhibitor Inhibits *VEGFR, RAf-1, BRAF, FGFR, etc* FDA approved for mCRC prev tx with 5-FU, oxaliplatin, and irinotecan

At what stage do you always do adjuvant chemotherapy for CRC

-Stage III and IV Only do surgery in stage IV if resectable, always surgery in stage III

Stage III CRC chemo AFTER surgery

-Standard is a *5-FU based* regimen for *6 months* after surgery. Note a big trial was released and some may consider 3 month for lower risk now. 1. FOLFOX (CIV 5-FU/LV/oxaliplatin) 2. Capecitabine (xeloda) + Oxaliplatin (CapeOx) *If oxaliplatin inappropriate* 1. 5-FU + LV (CIV 5-FU may be better with less hematologic toicity) 3. FLOX (BOLUS 5-FU/LV/oxaliplatin) 4. Capecitabine monotherapy If *MIS-H/dMMR/Lynch do FOLFOX or CAPOX +/- targeted therapy*

Prophylaxis for chemo with low emetogenic potential

-Start BEFORE chemotherapy -Any anti-emetic MONOTHERAPY will work *EXCEPT substance P/NK1 receptor antagonist* *Most common* -Zofran 8 mg PO -Prochlorperazine 10 mg PO

ACS screening recommendation with history of CRC in any first degree relative < 60 yo or 2 or more at any age

-Start at *age 40* or 10 years before youngest case *Colonoscopy Q5 years*

ACS screening recommendation with history of CRC ir adenomatous polyps in any 1st degree relative > 60 yo or in 2 2nd degree relatives of any age

-Start screening at age 40 -Screening as normal beginning age 40

Nonpharm for nausea and vomiting

-Stay *well-hydrated* -Eat smaller, more frequent meals through day -Peppermint candy, ginger tea, or other ginger based products -Referral to music therapy -Acupuncture/acupressure -Hypnosis/guided imagery

Medications that must be given with pemetrexed

-Steroid prior to infusion, day of AND day after to *minimize risk of rash* -Low dose *folic acid 7 days prior to treatment and 21 days post-treatment* -Vitamin *B12 injection during week BEFORE treatment EACH CYCLE*

Etiology of colocrectal cancer

-Strong association with *diet* -*K-RAS mutation* detected in 50% if CRC and adenomas -Deletion or inactivation of tumor suppressor genes - adenomatous polyposis coli (*APC gene*) in FAP, *loss of p53*, and deleted p53 in the colorecctal carcinoma (*DCC*) gene -Replication errors

Rituximb specifics in RA

-Studied and indicated *ONLY in combo with MTX* and only *after failing TNFi*

Orencia dosage forms

-SubQ -IV

Cimzia (certolizumab pegol) clinical pearls

-SubQ injection so rotate injection sites

DDIs with irinotecan (remember SN-38 metabolite)

-Substrate of CYP2B6 and *CYP3A4* -Contains *sorbitol* so do not use in patients with hereditary fructose intolerance

2018 PADIS Guidelines on Delirium

-Suggest NOT using haloperidol, atypical antipsychotics, dexmedetomidine, a statin, or ketamine to prevent delirium -Also do NOT suggest using routinely to treat Why? - evidence is really weak -Ont trial in haloperidol vs ziprasidone vs placebo found no difference in days alive without delirium or coma

H2RA role in stress ulcer *prophylaxis*

-Superior to sucralfate and *preferred over PPIs* due to theoretical PPI risks -Certain patients like those with *prior GI bleed should, HOWEVER, receive PPI* -Need more data to assess optimal dose for H2RA and PPIs *SUP-ICU and PEPTIC studies* is where this info comes from

Methotrexate clinical pearls

-Supplement with *folic acid 5 mg PO weekly* CI in pregnancy and breastfeeding - if used in breastfeeding, consider withholding for *> 24 hours* after low dose (< 20 mg) -CI in *chronic liver disease, alcohol use, and immunosuppressed (e.g. HIV or transplant)

IMPACT Trial

-Supported valganciclovir *900 mg X 200 days for HIGH RISK only* (D+/R-) *ONLY kidney transplant patients*

Anusol-HC form and site

-Suppository -Rectum only

Stage I-II typical NSCLC treatment options

-Surgery -Radiation -Chemotherapy offered in stage II ONLY due to small increase in OS -Clinical trial always an option

Treatment modalities for breast cancer

-Surgery -Radiation therapy -*NEOadjuvant chemotherapy* - this is important -Adjuvant *Chemo OR endocrine therapy* (usually both) -Targeted therapy

Virologic cure of HCV: Definition

-Sustained virologic response (*SVR*) No detectable viral load at end of therapy AND *12-24 weeks later*

General important S/S of RA

-Symptoms of an inflammatory process -Arthralgia/stiffness > 6 weeks Frequently *symmetric and polyarticular involvement* Very different than a non-inflammatory process

Misoprostol MOA and PK

-Synthetic PGE1 analog that is protective and substitutes for PG decreased with drugs like NSAIDs that inhibit PG synthesis. Inhibits gastric acid secretion and protects mucosa. *PK* -Onset is 2-3 hours and lasts > 3 hours -DOSE DEPENDENT effects - (200 mcg PO Q6H with food) -Must take *with FOOD* -Caution in renal impairment as it is *80% excreted in urine*

If someone is having major GI symptoms after transplant what should you order/check?

-Tacrolimus level -Trial of holding mycophenolate -GI biopsy -CMV-PCR -Med history

Antiestrogens available

-Tamoxifen -Fulvestrant

Clinical pearls for steroids in IBD

-Tapering off, alternate day dosing, rectal, and budesonide can reduce risk of AEs -Withdrawal must be GRADUAL -Taper systemic roids over *2-4 weeks* -For taper convert systemic steroid to oral prednisone -Treatment of steroid induced hyperglycemia, swelling, and HTN can be done -Osteoporosis prevention may be prescribed - *Calcium, vit D, or bisphosphonates* -AVOID *CYP3A4 inhibitors* - can increased systemic effects

Which HBV drugs must be combined with TDF or ADV in cirrhosis?

-Telbivudine -Lamivudine

Which antiviral should be AVOIDED completely in HIV co-infected patients?

-Telbivudine (LdT)

Signs of RA on physical exam

-Tenderness -Warmth and swelling over affected joints (usually distal extremeties)

When could you consider adding insulin to a TPN?

-The BG elevation is due to the *PN ONLY* Not a effect of other things like critical illness, T1DM, or high dose steroidds

Cytomegalovirus background

-The MOST common opportunistic viral pathogen -Without prophylaxis usually occurs in *first 3 months after transplant* *Diagnosis* 1. Viremia (detectable virus in blood) 2. Symptoms 3. End organ damage (direct effects) *Indirect immunomodulatory effects* also matter! Associated with significant morbidity and mortality

Alemtuzumab MOA

-The most immunnosuppressive drug available -Blocks *CD52 receptor* on multiple immune cells and induces cell lysis Essentially wipes out the entire immune system

Irinotecan metabolism

-Topo 1 inhibitor that is activated to *SN-38* which has *100-1000 fold greater antitumor activity* -Then SN-38 undergoes *glucuronidation* by *UGT1A1* - homozygotes with the *UGT1A1 star 28 allele have INCREASED exposure to SN-38* (prevalence around 10%)

Irinotecan MOA

-Topo I irreversible inhibitor -Results in cleavable complexes and strand breaks -Malignant cells may have higher concentrations of topo I

Who is at highest risk of HAV in US?

-Travelers to countries with high HAV incidence -Use of illegal drugs, especially *IVDA* -*Chronic liver disease* Others include male homos, clotting factor disorders, living with person infected, oral-anal sexual contact with person with HAV

AASLD/IDSA HCV guidelines for HCV treatmetn

-Treat *ALL patients* with chronic HCV infection EXCEPT those with short life expectancy that cannot be remediated by other therapies

Abx therapy in septic shock

-Try to figure out source -Collect cultures *PRIOR* to initiating abx -Collect *at least 2 sets of cultures* (aerobic and anaerobic) WITHIN 1 HOUR - broad spectrum

Inflammatory bowel diseases and colorectal cancer

-Ulcerative colitis increases risk by *30X* -Crohn's disease slightly lower than UC *1-2% of cases*

Zepatier (Grazoprevir/Elbasvir) clinical pearls

-Use *contraindicated with moderate-severe hepatic impairment (Child Pugh B or C)* -Use contraindicated in patients receiving *OATB1B1/3 inhibitors, strong CYP3A4 inhibitors, and efavirenz* -Genotype *1A: Testing for the presence of virus with NS5A resistance-associated polymorphism is recommended* -ALT elevations: Perform hepatic lab testing prior to therapy, at treatment *week 8* and as clinically indicated

TAF contraindications

-Use with potent BCRP or PGP inducers (e.g. phenytoin and rifampin) -CrCl < 15 mL/min

Everolimus (Afinitor, Zortress)

-Used *with exemestane* (steroidal AI) for ER+, HER2- patients that progressed on letrozole or anastrozole -*mTOR inhibitor* that inhibits activation *P13K/Akt/mTOR* pathway which can contribute to endocrine resistance in BC *Side effects* -Mucositis -*Rash* -Diarrhea -Fatigue -Infection -Increased LFTs -*Hyperglycemia*

Alpelisib (Piqray)

-Used *with fulvestrant* (SERM) -For *HR+/HER2- PIK3CA-mutated* breast cancer following progression on or after endocrine based regimen -A *PI3K inhibitor* *Adverse effects* -SJSs -*Hyperglycemia* -Renal dysfunction -N/V -Diarrhea -*Rash* -LFT elevations -Anemia -Alopecia *Prophylax with cetirizine for rash* *DDIs* -CYP3A4 substrate avoid with inhibitors -BCRP sub avoid with inhibitors

Pemetrexed (Alimta) place in therapy for NSCLC and SCLC

-Used commonly in BOTH -NOT used in *Squamous cell cancers (ineffective)*

Guideline stance on steroids in septic shock

-Used if *fluid resuscitation and vasopressor have been initiated* -Usually *Hydrocortisone IV 200 mg/day as *Q6H 50 mg boluses*

Spontaneous breathing trials (SBTs)

-Used to determine if patient is ready to breathe on own *Decreases* -Time to extubation -Ventilator time and complication

Hand foot syndrome prevention and treatment

-Usually *hand creams* (keep moisturized) -Possibly oral vitamin B6

S/S of CRC

-Usually asymptomatic *Could be* -Rectal bleeding -Change in bowel habits -Vague abdominal discomfort -Abdominal distention -N/V, abdominal discomfort due to obstruction, perforation, or bleeding -*Iron deficiency anemia*

PUD-induced ulcer acute bleeds background

-Usually occur *before* hospital admission -Bleeding usually from single vessel -Mortality rate *10% with bleeding*

Stress-related mucosal bleeding background

-Usually occurs in ICU patients during hospitalization -Results from *mucosal ischemia* due to *decreased gastric blood flow* usually due to splanchnic hypoperfusion -Usually occur from *superficial* mucosal capillaries -Incidence in ICU patients is 1.5-8.5% and up to 15% in those not receiving stress ulcer prophy. < 1% may have GI perforation due to SRMB is associated with *increased mortality (~50%) vs non-SRMB (9%)

Clinical presentation of lymphoma

-Usually older adults -Peripheral *lymphadenopathy* (80% of patients have lymph involvement above diaphragm - neck, axillary, thymus) -Symptoms based on bone marrow and extranodal involvement *B symptoms (40%)* -Fever -Night sweats -WEIGHT LOSS -Fatigue -Malaise -Pruritis

Options for CMV prophylaxis

-Valganciclovir 450-900 mg PO QD -Gancicylovir 5 mg/kg IV daily -Valacyclovir d2 g PO QID -*CMV IVIG*

TNF inhibitors in pregnancy and lactation

-Vary by *trimester* - there is a risk vs benefit discussion needed -In lactation generally considered *SAFE* due to very little penetration

Short term consequences of pain

-Vasocontriction -Increased BP -Increased HR -*Decreased tissue perfusion* -Increased BG -Increased *muscle breakdown*

Which drugs should be avoided with acid suppressing agents?

-Velpatasvir (Epclusa) -Ledipasvir (Harvoni) -Voxilaprevir (Vosevi)

Cyclosporine, TAC, CRL, and ERL PK

-Very *hydrophobic* -Substrates for PGP and CYP3A4/5 -*Poor oral absorption* -High inter and intra patient variability -Drug interactions, so *ALWAYS TDM* -*High plasma protein binding* -Extensive hepatic metabolism

Monitored transplant drug properties (why they

-Very hydrophobic -Substrates of PGP and CYP3A4/5 -Poor oral absorbtion (*~25% with CsA and TAC*) and high inter and intrapatient variability -High plasma protein binding -Extensive hepatic metabolism

Propofol related infusion syndrome (PRIS)

-Very rare, but high mortality associated *Risk factors* -Dose > 80 mcg/kg/min for > 48 hours -Critical illness -Inadequate carbohydrate delivery -Age < 18 *Clinical presentation* -Severe metabolic acidosis -Rhabdomyolysis -Acute renal failure -CV collapse -HYPERkalemia Promptly discontinue, start RRT, ECMO option

Vitamins absorbed in the proximal jejunum

-Vitamins A and B -Folic acid -Iron -Disaccharides

Is vomiting or nausea easier to prevent/treat?

-Vomiting

Antihistamine site of action for vomiting

-Vomiting center in pyloric area of stomach

NS3/4A protease inhibitors

-Voxilaprevir -Glecaprevir

When do you use vasopressors in septic shock picture?

-When appropriate fluid admin FAILS to restore MAP and organ perfusion

When do you use neupogen for prevention of febrile neutropenia?

-When risk is > 20% -Risk is based off chemo regimen or other patient specific factors

When are ulcers considered refractory to treatment?

-When symptoms, ulcers, or both continue *beyond 8-12 weeks* Options then: -Use higher doses of PPI in H. pylori negative ulcers -Use eradication therapy in H. pylori pos ulcers -Can *continue PPI long term*

Low emetogenic chemos

-Without prophy 10-30% of patients will have N/V

Moderately emetogenic chemos

-Without prophy 30-90% of patients will have n/v -If you had two moderates you would almost treat it as high

Highly emetogentic chemos

-Without prophy >90% of patients will ave N/V -ALWAYS require multiple agents for prophylaxis

Corticosteroids place in transplant

-Work non-specifically as anti-inflammatory and also inhibit lymphokine production by APCs (IL-1) *Induction* -High doses tapered quickly *Maintenance* -Based on rejection risk and tolerability *Rejection* -High doses for SHORT period of time (PULSES)

Vitamins and trace elements that can be measured (starred)

-Zinc -Selenium -Copper -*Manganese* -Iron -Vitamin Bs (folic acid, thiamine) -Vitamin D -Vitamin A Evaluate components of and *adjust nutritional support based on levels*

Vasopressin infusion rate

0.03 U/min

Protein requirements in renal dysfunction

0.8 - 1 g/kg (not dialysis)

Treatment strategies in septic shock

1. *First try fluid resuscitation* 2. Vasopressors 3. Antimicrobial therapy and source control 4. Inotropic therapy 5. Steroids 6. Blood product admin 7. Mechanical ventilation 8. Sedation, analgesia, NM blockade - *INTUBATE* 9. Glucose control 10. Renal replacement 11. DVT prophylaxis 12. Stress ulcer prophylaxis

Poor prognostic risk factors of PUD-induced GI bleed

1. > *60 years of age* 2. Comorbid conditions (CHF, renal failure, metastatic cancer) 3. High transfusion requirements 4. Ongoing blood loss 5. Presence of hypovolemic shock 6. Prolonged *PT time* 7. Erratic mental status

Who should be TESTED for H. pylori infection

1. ACTIVE or HISTORY of PUD (gastric or duodenal) 2. Gastric mucosa-associated lymphoid tissue (MALT) 3.Post-gastric cancer endoscopic resection There are also some controversial indications that wee do not need to know like unexplained iron deficiency anemia

When to hold val/gancicyclovir therapy due to side effects

1. ANC drops below 0.5 (500) 2. Plts drop below 25,000 (25) 3. Hgb drops below *8* These are pretty severe neutropenia, thrombocytopenia, and anemia

Opioid withdrawal can occur when?

1. Abrupt cessation of high dose opioid 2. Continuous infusion *> 7 days*

PPI utility and dosing

1. Achieve intragastric pH of > 6 2. *HIGH DOSE PPI = continuous IV infusion* 3 *Standard dose PPI = oral PPI twice or once daily*

CAM-ICU Features (4)

1. Acute change or fluctuating course of mental status 2. Inattention 3 Altered level of consciousness 4. Disorganized thinking CAM-ICU Positive = Delirium

Indications for deep sedation in the ICU

1. Acute respiratory distress syndrome (ARDS) - probably the most common reason. Must use NM blocker and ventilator 2. Severe traumatic brain injury (TBI) - agitation can increase cranial pressure 3. Refractory status epilepticus (burst suppression w/ continuous EEG) 4. Therapeutic hypothermia (short term to manage shivering < 48h) 5. Agitation where patient could case harm to self or others. ONLY if necessary

Poor prognostic factors for DLBCL

1. Age > 60 2. ECOG of 2 or more 3. *Elevated LDH* 4. *2 or more extranodal sites* 5. Richter syndrome (CLL transforms to lymphoma)

Strong evidence risk factors for delirium

1. Aging 2. Dementia 3. Hypertension 4. Pre-ICU emergency surgery or trauma 5. APACHE II score 6. *Mechanical ventilation* 7. *Metabolic acidosis* 8. Delirium on prior day 9. Coma Moderate evidence for multi system organ dysfunction being a risk factor

Roles of macrophages

1. Antigen presenting cells 2. Surveillance of antigens *Operate by:* -Phagocytosis -Binding and removing with others -Release of toxic chemicals (NO, TNF, H2O2, histamine)

Areas in which RA most commonly presents

1. Articular RA (60%) 2. Extra-articular (40%) -*Rheumatoid nodules (20%)* -Vasculitis from *splinter hemorrhages* to distal gangrene -Pulmonary fibrosis (tobacco worsens) -Sjogren syndrome -Anemia of chronic disease *Rare* -Pyoderma gangrenosum -Pericarditis and arrhythmias -Felty syndrome -Peripheral neuropathy -Glomerulonephritis and interstitial renal disease

3 DDI Management Strategies

1. Avoid the combination and use an alternative 2. No dose adjustment, but monitor levels and adverse effects - often for *moderate interactions* 3. Adjust the dose empirically *DO NOTHING if not clinically significant*

Validated assessment tools for Assessing Pain

1. Behavioral Pain Scale (BPS) - 3-12 point scale 3 being no pain 2. Critical Care Pain Observation Tool (CPOT) - 0-8 scale with 0 being no pain

Herbals and OTC for RA that have killed people

1. Borage 2. Thunder God vine

Review: Activation of T killer cells (CD3+, CD8+)

1. Cells recognize *class I MHC* AND *CD80/86* and become activated. In the presence of CTLA4 (e.g. cancer or self), T cell will not bind CD80/86, thus not be activated 2. KIller T cell kills the antigenic or infected cell

Review: Activation of T killer cells (CD3+, CD8+)

1. Cells recognize *class I MHC* AND *CD80/86* and becomes activated. In the presence of CTLA4 (e.g. cancer or self), T cell will not bind CD80/86, thus not be activated 2. KIller T cell kills the antigenic or infected cell

Most common radiochemotherapy regimens for NSCLC in the US

1. Cisplatin + etoposide (topo IIi) 2. Carboplatin + paclitaxel Becoming more popular...Cisplatin + pemetrexed For stage 3 usually add an immunotherapy (e.g. durvalumab, tagrisso, nivolumab) if patient has progression after 2 cycles of Pt based regimen

Validated assessment tools for delirium in the ICU

1. Confusion Assessment Method-ICU (CAM-ICU) 2. Intensive Care Delirium Screening Checklist (ICDSC) - 4 or more = delirious

AVOID NSAIDs with these drug classes due to increased risk of GI perforation

1. Corticosteroids 2. IL-6 RAs (tocilizumab and sarilumab) 3. JAK inhibitors (tolfacitinib and baricitinib) Avoid all in setting of diverticulitis

NSAID induced GI bleed treatment

1. DC NSAIDs (+ aspirin) 2. Start *HIGH DOSE PPI therapy* - PPI preferred due to lower risk of rebleed and more rapid ulcer healing AFTER ABOVE: 1. Start standard dose PPI 40 mg *BID* for *14 days* followed by standard dose PPI 40 mg *once daily* *LONG TERM* After GI bleed resolve: 1. MUST address NSAID and aspirin use -If no clear indication for NSAID *DO NOT RESUME* -If NSAID required, *PPI should be continued LONG TERM* while on NSAID therapy

Virologic treatment response definition in HBV

1. Decreased serum HBV DNA to undetectable 2. Loss of HBeAg in patients who were HBeAG+

Treatment of patients with ACTIVE NSAID-related ulcer

1. Discontinue NSAIDs if possible and switch to tylenol or nonacetylated alicylate (e.g. salsalate or trisalicylate) if possible If NSAID needs to be continued: Try *lower dose* and switch to a more selective COX-2 inhibitor* - consider CV and GI bleed risk table. Basically use celecoxib if GI risk is > CV risk and naproxen if CV risk is > GI 2. *PPI is drug of choice* with continued NSAID use - misoprostol if allergy.

Acute renal failure by TLS

1. Due to hyperuricemia and formation of uric acid crystals in tubules 2. Hyperphosphatemia - CaPhos deposits in tubules 3. Tumor infiltration in kidney 4. Tumor associated obstructive uropathy 5. Drug associated nephrotoxicity 6. Acute sepsis

Vaccines for HepB

1. Energix-B 2. Recombivax 3. HEPLISAV-B Energic and Recombivax are routine for 0-18 and people with risk facctors HEPLISAV for adults (>18) and people with risk 2 or 3 doses for primary series provide at least 20 year to lifelong protection *HIGHER DOSES IN HD PATIENTS* *Combo vaccines* 1. PEDIARIX (HBV with TDAP and Polio) 2. TWINRIX (HAV-HBV combo)

Idelalisib (Zydelig, IL17i) BBW

1. Fatal or serious hepatotoxicity 2. Fatal and severe diarrhea or colitis 3. Fatal and serious *pneumonitis* 4. Fatal and serious *intestinal perforation*

Idelalisib BBW

1. Fatal or serious hepatotoxicity 2. Fatal and severe diarrhea or colitis 3. Fatal and serious *pneumonitis* 4. Fatal and serious *intestinal perforation*

Signs and Symptoms of CMV infection

1. Flu-like and mononucleosis-like syndrome -Fever -Malaise -*Leukopenia* -*Thrombocytopenia* *Tissue invasive disease* - Nephritis, hepatitis, carditis, pneumonitis, pancreatitis, colitis, retinitis (end-organ damage) -*Colitis is common and leads to persistent diarrhea, vomiting, and rare perforation*

FLAG Regimen (MiMed LOVES using this - theoretical advantage is similar CR and CRi rates to 7 + 3 but better tolerability)

1. Fludarabine 30 mg/m2 on days *2-6* 2. Cytarabine 2,000 mg/m2 over 4 hours starting AFTER fludarabine on days 2-6 3. G-CSF *SQ* daily starting day 1 until count recovery Slides say that this is ideal for patients with *cardiac history* or *secondary/t-AML* - this is because we want to avoid anthracyclines in pts with cardiac problems and sAML has super poor prognosis regardless of treatment (survival median usually 6-8 months from dx). At MImed we are doing a multi-center trial comparing FLAG to 7 + 3 because they believe FLAG is better tolerated with similar remission rates and OS. If people are going to have a short life, they might as well not be throwing up and miserable their last days.

The BIG 3 treatment strategies in septic shock

1. Fluid resuscitation - *crystalloid within first 3 HOURS* 2. Vasopressors 3. Antimicrobial therapy and source control 4. Inotropic therapy 5. Steroids 6. Glucose control

JAKi general warnings and side effects

1. GI perforation: Increased risk with NSAIDs, hx of diverticulitis, prior GI bleed 2. Neutropenia - Decreased WBC, hold if *ANC < 1,000* 3. Anemia is rare, but if Hgb < 8 or drops > 2 from baseline HOLD *AVOID in pregnancy and lact* Screen for infections and monitor for *SKIN CANCER* periodically

Endoscopic tests of choice for H. pylori

1. GOLD STANDARD = *histology*, but results are not immediate so *not recommended for initial dx*. Tests for an *active H. pylori infection* and is > 95% sensitive AND specific 2. *Biopsy (rapid) urease* - test of CHOICE when doing endoscopy. > 90% sensitive and specific and is easily performed with *rapid results* (< 24 hours). Tests for *active infection only*

Induction CMV TREATMENT

1. Ganciclovir 5 mg/kg IV *Q12H* 2. Valganciclovir 900 mg BID Pick and do *2 weeks* or longer if needed for clinical resolution and viral clearance (*3 weeks in VICTOR trial*)

Maintenance CMV treatment

1. Ganciclovir 5 mg/kg IV *Q24H* 2. Valganciclovir 900 mg PO *QD* Note same dosing, just longer frequency Duration usually *1-3 months* (4 weeks in VICTOR trial), but main thing is to make sure patient is asymptomatic and viral load is undetected

Mycophenolate metabolism

1. Gluccuronidated in liver to MPAG 2. Hydrolyzed to MPA in intestin after bile excretion 3. MPA absorbed into bloodstream

Drugs that directly stimulate neutrophil and macrophage production

1. Granulocyte colony stimulating factor (GCSF) aka neupogen or neulasta (filgrastim) 2. Granylocyte-macrophage colony stimulating factor aka the mostims (e.g. sargramostin)

Treatment of infectious complications with TPN

1. HOLD TPN and remove catheter 2. Treat ifection 3. Replace line and restart CPN with possible *In the interim supplement with peripheral fluids - dex and electrolytes*

S/S of stress-related mucosal bleeding (SRMB)

1. Hematemesis 2. Melena Signs: -Low Hgb and hematocrit -If high blood loss (hypovolemic) patient mat be hypotensive and dizzy

Consolidation therapy for AML

1. HiDAC most common (High dose arabinoside cytarabine). Give *1-3 g/m2* (remember 100-200 mg/m2 is for 7+3) 2. FLAG consolidation (there are multiple other options UMich just does this most) 3. Allogenic (from donor) stem cell transplant - only way to "cure"

Dietary risk factors of colorectal cancer

1. High fat 2. Low fiber 3. Pyrolysis products like benzopyrenes that are a *carcinogenicc byproduct of fried meats* 4. Red and processed meats

FLOX

1. IV leucovorin over 2 hours 2. 5-FU 500 mg/m2 IVP after 1 hr of LV infusion *weekly x 6 weeks* followed by a 2 week break 3. Oxaliplatin 85 mg/m2 IV on weeks 1, 3, and 5 of each *8 wk cycle X 3 cycles*

Diagnosis of lung cancer

1. Imaging: Can do CT, CXT, PET, or *MRI*. Usually start with CT w/contrast 2. Biopsy (and pathology) to establish tissue diagnosis 3. Labs (CBC and PLT, Comprehensive metabolic panel)

Acute leukemia (e.g. AML) Classification

1. Immature cells! 2. Rapid onset of symptoms (seemingly random jump in WBCs) 3. Progresses in weeks to months = poor prognosis 4. Aggressive 5. *Curable* - although totally dependent on type for success rate

Things that can cause splachnic and mucosal hypoperfusion and result in SRMD

1. Increased catecholamines (and subsequant lower CO) 2. Hypovolemia 3. Increased vasoconstriction 4. Pro-inflammatory cytokine release (e.g. sepsis) *Lowers* -Bicarb secretion -Mucosal blood flow -GI motility -Protective factors -Acid back-diffusion

Impact of delirium on health outcomes

1. Increased mortality rate at 6 months 2. Longer ICU stay and *longer duration on ventilation* 3. *Long term cognitive impairment* at 3 and 12 months following ICU admission (most well known study)

Belatacept major safety issues

1. Increased risk of *PTLD and PML*, no longer requires REMS 2. Unexplained feveer, night sweats, fatigue, weight loss, anorexia 3 Watch for new or change in neurologic, cognitive, or behavioral S/S *Post-transplant lymphoproliferative disorder (PTLD)* -Involves CNS mainly -CI if recipient *EBV serostatus* negative or unknown *Progressive multifocal leukoencephalopathy (PML)* -Rare, serious CNS infection by JC virus

Biggest concerns with PPI use

1. Increased risk of CAP, *C. diff infection*, salmonella, and/or campylobacter - most data for CDI 2. Increased risk of hip, wrist, and spine fractures with *HIGH DOSE PPI long-term* related to lower Ca absorption 3. Increased risk of *hypomagnesemia* (symptomatic and asymptomatic) -Most cases occurring with long term PPI therapy but can occur in as little as 3 months 4. Vitamin *B12 deficiency and ANEMIA* may occur with prolonged use. Due to impaired absorption of protein bound vitamin B12

Virologic relapse definition in HBV

1. Increased serum HBV DNA of 1 log10 IU/mL after DC of treatment in at least *2 determinations more than 4 weeks apart*

Treatment scheme for AML

1. Induction chemo -7+3 best now vyxeos is out (liposomal combo form) and is said to have better outcomes - debatable -FLAG -CLAG -HMA based regimen (older patients that cannot tolerate) 2. Do bone barrow biopsy to assess response 3. No response = refractory disease, CR means *< 5% blasts on repeat bone marrow*

Sepsis criteria

1. Infection + end organ dysfunction 2. >/= 2 point change in SOFA score Quick SOFA = Resp rate > 22, AMS, and SBP < 100

Less intensive chemo regimens for stage IV CRC

1. Infusion of 5-FU or capecitabine +/- bevacizumab 2. Cetuximab or panitumumab 3. MSI-H -Nivolumab or pembrolizumab -Nivolumab + ipilimumab

Rituximab concerns

1. Infusion reactions - usually premedicate with tylenol AND benadryl 30-60 min before infusion 2. Can reactivate HepB, thus screen before 3. Infection risk during and 1 year post tx (all infection types) 4. RARE: *Progressive multifocal leukoencephalopathy (PML)*

Stages of Sepsis

1. Initiation - recognition of pathogen, infection 2. Activation of inflammation - primary and secondary mediators 3. Endothelial activation (where PLT comes in) 4. Activation coagulation/impaired fibrinolysis 5. Microvascular *thrombosis*, ischemia 6. Organ failure

Drugs that can stimulate T cells

1. Interleukins - IL-2 agonism 2. Interferon (stimulates T cells and a lot more)

FOLFIRI regimen for stage IV CRC

1. Irinotecan 180 mg/m2 IV + LV 400 mg/m2 IV 2. 5-FU 400 mg/m2 IV bolus then 2400-3000 mg/m2 IV continuous over 46 hours

mTOR inhibitor general side effects

1. Leukomenia, anemia, and thrombocytopenia (like mycophen) 2. Hypercholesterolemia and hypertriglyceridemia 3. *Interstitial lung disease* 4. *Peripheral edema* 5. *Impaired wound healing* and dehiscense 6. *Mouth ulcers* Used in place of mycophenolate or CNI

LOAD regimen for PUD

1. Levofloxacin *350 mg* QD 2. PPI (O for omeprazole *double dose*) 3. Nitazoxanide (Alinia) 500 mg BID (new and specific) 4. Doxycycline 100 mg QD *7-10 day regimen*

Areas to look at in physical exam for malnutrition

1. Loss of SQ fate (triceps and chest) 2. Muscle wasting (quads and deltoids) 3. Edema (ankle and sacral) 4. Ascites Rated as mild, moderate, or severe

Goals of RA therapy

1. Low disease activity ("treat to target" T2T strategy) - treat until remission then visit *every 3 months* 2. Improve quality of life 3. Prevention and management of adverse drug reactions

Goals of therapy in RA

1. Low disease activity, treat until remission and do visits every *3 months* 2. Improved QOL 3. Prevention and management of adverse drug reactions

Early (< 6 months) or established (6+ months) *DMARD Naive* treatment algorithm for RA (low to high disease activity)

1. Low to high disease activity: DMARD (MTX preferred) +/- prednisone 2. If moderate-high disease activity and above did not work: Combine DMARD or TNFi +/- MTX or non-TNFi biologic +/- MTX or Tolfacitinib +/- MTX *Failure of single TNFi* -Use Non-TNF biologic +/- MTX or different TNFi +/- MTX -If still moderate-high disease activity can do Tolfacitinib +/- MTX *Non-TNF biologic failure* -Try another non-TNFi biologic +/- MTX -TNFi in TNFi treatment naive or Tofacitinib +/- MTX *Assess efficacy and consider major tx decisions every THREE MONTHS*

Good for Ca-Phos solubility (decreases ppt chance)

1. Lower pH (why we have to be careful with AA concentration) 2. Ca gluconate 3. Shorter time in solution (expire < 24H) 4. LOWER temperature 5. Separate Ca and Phos when compounding

Most high risk transplants for CMV infection

1. Lung and small bowell 2. Heart and pancreas 3. Kidney and liver

Fluid resuscitation goals in septic shock

1. MAP > 65 mm Hg 2. Normalization of *lactate levels* 3. HR, BP, arterial oxygen saturation, resp rate, temperature, urine output, cardiac output

Purposes of Parenteral nutrition

1. Maintain or gain weight 2. Preserve or restore lean body mass 3. Support anabolism and nitrogen balance 4. Correct nutritional deficiencies

Steps to take *within first hour* of sepsis

1. Measure lactate. Remeasure if initial lactate > 2 mmol/L 2. Obtain cultures PRIOR to abx if possible 3. Administer broad spectrum abx 4. Begin rapid administration of 30 mL/kg of crystalloid for hypotension OR lactate level > 4 5. Administer vasopressors if patient is hypotensive during or after fluid resuscitation to maintain MAP > 65

Monitoring of levels for CMV infection treatment

1. Monitor *SCr* for dose adjustment 2. CBC 2/diff for side effects: Hold if ANC < 0.5 (500), Plt < 25,000 (25), or Hgb < 8 3. Symptoms and end-organ induction 4. CMV-PCR at *at least 2 week induction* 5. Ganciciclovir resistance genotyping ONLY if slow clinical response or no viral clearance

Pre-emptive therapy for CMV

1. Monitor via CMV-PCR for *1-2 weeks* and treat if viral load is detected *Universal prophylaxis* -Valganciclovir 450-900 mg PO QD most common -Gangicyclovir 5 mg/kg IV QD also option (inpatient only)

Chronic leukemia (e.g. CML) Classification

1. More mature cells 2. Gradual onset of symptoms 3. Progresses over years 4. Less curable than acute 5. Treatment goal is often to delay progression and manage symptoms

AML Pathophysiology

1. Mutations occur and myeloid stem cells differentiate into myeloblasts as normal, however the myeloblasts *DO NOT mature* into health WBCs (e.g. basophils, eosinophils, neutrophils, monocytes) 2. These stem cells become abnormal stem cells (blasts) that build up in the bone marrow and crowd out healthy white blood cells, red blood cells, or platelets and prevent their development and differentiation (hence why we often find neutropenia, thrombocytopenia, anemia, etc)

Side effects of adjuvant chemo in breast cancer

1. Myelosuppression 2. N/V 3. GI-severe mucositis or stomatitis and diarrhea needing hospitalization (higher w/ 5-FU 4. Neurologic (taxanes) - neuropathy, myalgia, arthralgia 5. Weight gain (avg 2-6 kg) AC < CMF 6. Hair loss 7. Ovarian failure *CMF > AC* - increased risk of osteoporosis and hot flashes 7. Cardiotoxicity - acute arrhythmia but chronic can cause direct cardiomyopathy. Risk with older age, higher cum dose, pre heard disease, co-admin of paclitaxel or trastuzumab. *Zinegard antioxidant to protect* 8. Secondary cancers 9. Fatigue and quality of life 10. Hypersensitivity reactions with *taxanes* - premedicate with antihistamines and steroids. Docetaxel = fluid accumulation

IL-5 inhibitor (e.g. mepolizumab) warning

1. Opportunistic infections 2. *Parasitic (helminth) infection* Apparently eosinophils are big in killing off parasites

CapeOx +/- bevacizumab for stage IV CRC

1. Oxaliplatin 130 mg/m2 IV day 1 2. Capecitabine 850 mg/m2 PO BID x 14 days 3. Bevacizumab 7.5 mg/kg IV Q3Wk

mFOLFOX6

1. Oxaliplatin 85 mg/m2 over 2 hours + LV 400 mg/m2 over 2 hours 2. Follow with 5-FU 400 mg/m2 IV then 2400 mg/m2 over 46-48 hours Repeat every *2 weeks for 12 weeks*

Concomitant therapy regimen (FIRST LINE) for PUD

1. PPI (standard dose) 2. Clarithromycin 500 mg BID 3. Amoxicillin 1 g BID 4. *Nitroimidazole 500 mg BID* 10-14 day regimen Has less degree of clarithromycin resistance vs clarithromycin triple therapy

Clarithromycin triple therapy regimen

1. PPI (standard or double dose) 2. Clarithromycin 500 mg BID 3. Amoxicillin 1 g BID ALL BID - *!4 DAY regimen* CAN replace amoxicillin with metronidazole 500 mg TID in PCN allergic patients

Levofloxacin sequential regimen for PUD

1. PPI (std OR double dose) 2. Amoxicillin 1 g BID THEN 1. PPU 2. Amoxicillin 3. Levofloxacin 500 mg QD 4. Nitroimidazole 500 mg BID

Levofloxacin triple therapy for PUD (suggested not preferred)

1. PPI (std dose) 2. Levofloxacin 500 mg QD 3. Amoxicillin 1 g BID *10-14 days total*

Common types of acute nonvariceal GI bleeds

1. PUD-induced bleeding: Bleed from chronic ulcers 2. Stress-related mucosal bleeding (SRMB): Bleeding from stress-related mucosal damage (SRMD)

TPN administration options

1. Peripherally (PPN) 2. Centrally (CPN or TPN) through PICC line *Not preferred peripherally because TPNs are hyperosmolar and can cause thrombophlebitis* - if peripheral limit to max *900 mOsm/L* to prevent (problem: this limits to 1000-1500 cals max)

Treatment of IBD in pregnancy

1. Preconception counseling needed - preferably induce disease remission *3 months prior* 2. Sulfsalazine + folic acid 1 mg BID preferred -Dexamethasone and MTX are catagory X -AZA and 6-MP should be avoided -Avoid prolonged metronidazole If biologics, *infliximab only 1st and second trimester*, *stop humira 8-10 wks before delivery*, do not use natalizumab 3. If breastfeeding keep *prednisone < 40 mg/day* and avoid metronidazole and cyclosporine for sure

POOR prognostic factors for AML

1. Prior MDS/malignancy (sAML or tAML) 2. *FLT3+* 3. Poor cytogenetics - BCR-ABL t(9;22) mutation, inv(3), t*11q23), -5 or del(5q); -7

Goals in sedation management (4)

1. Promote analgosedation - first treat pain before just saying a patient is agitated 2. Minimize sedation - want responsive, communicativee patients. Avoid prolonged, deep sedation 3. Frequently re-assess sedation to optimize management 4. Awakening trials (usually each day). Turn off sedation and wait until patient is awake and can follow instructions or agitated. *Restart sedation at half prior dose. Often coordinated with breathing trial* (many studies showing better outcomes)

Measures to PREVENT breast cancer

1. Prophylactic mastectomies -Decrease risk by *90%* 2. Bilateral oophorectomies to decrease estrogen exposure, not 100% 3. Medications = endocrine therapy - Tamoxifen trial negatory -Raloxifene MAY reduce *invasive breast cancer and lower thromboembolic events*, but nonsig higher risk of noninvasive breast cancer

Treatment approach of acute *non-variceal GI bleed*

1. Provide *volume resuscitative measures: IV bolus of NS or *blood if Hgb < 7*. Should do a *diagnostic endoscopy *within 24 hours* to ID source of bleed, assess risk, and *provide tx intervention endoscopically* 2. Provide endoscopic intervention *AND antisecretory therapy* to prevent GI rebleeding. Note that antisecretory therapy here DOES NOT replace endoscopic intervention and intragastric pH *> 6* is needed to promote hemostasis and clot stability

Pancreas or Kidney/Pancreas transplant recommendation at UM

1. Rabbit ATG induction for ALL patients Tacrolimus, mycophenolate, and prednisone

Kidney transplant recommendation at UM

1. Rabbit ATG induction if high immunologic risk. Tacro, mycophenolate mofetil, and prednisone tapered to 5 mg/day 2. If very low immunologic risk (small subset) do steroid avoidance (5 days)

Steps in adaptive immune response

1. Recognition of foreign antigen by *circulating Ab* 2. CD20+ (B cells) are activated to make specific antibody - T-helpers bind to MHC-II on B cells and release signalling molecules that activate or trigger differentiation of B cells to plasma cells or memory cells 3. Antigen specific receptors are expressed on B cells (display MAB), T cells (CD8+ killer), and helper T cells (CD4+) that recognize antigen in future

Steps in adaptive immune response

1. Recognition of foreign antigen by *circulating Ab* 2. CD20+ (B cells) are activated to make specific antibody -Bs activate T helpers, which become plasma cells that pump out Ab 3. Antigen specific receptors are expressed on B cells, T cells (CD8+ killer), and helper T cells (CD4+) that recognize antigen in future

Review: Activation of T helper cells (CD3+, CD4+)

1. Recognize Class *II* MHC [resented on APCs (macrophages, B-cells, etc) 2. Helper T cells release signalling molecules that activate T killer cells, B cells to produce Ab, and macrophages

Review: Activation of T helper cells (CD3+, CD4+)

1. Recognize Class *II* MHC [resented on APCs (macrophages, onokines, etc) 2. Helper T cells release signalling molecules that activate T killer cells, B cells to produce Ab, and macrophages

HCQ Precautions in geneeral

1. Renal and hepatic impairment - there are no dose adjustments, but monitor. Accumulation is theoretical and not studied 2. GI disorders - can already cause GI distress, be careful 3. *Exacerbates psoriasis!* -small risk of SJS - advise patients to report any unexplained rashes while taking 4. Porphyria - different than others because both *exacerbates AND treats*

Opioid safety concerns

1. Respiratory depression - especially in spontaneously breathing pts 2. Hypotension - can increase parasympathetic activity and cause vagal mediated bradycardia 3. N/V from stimulation of CTZ (less in ICU pts) 4. Intestinal hypomotility - contipation or ileus. Start *bowel regimen and feed ASAP to prevent* 5. Tachyphylaxis

MAJOR risk factors for SRMB

1. Respiratory failure: Especially if on mechanical vent *> 48 hours* (OR 15.6) 2. Coagulopathy: INR *> 1.5 and or PLT < 50,000* (OR 4.3)

Risk scoring tools for PUD-induced GI bleed

1. Rockall score: includes two assessments, both *clinical score and endoscopic score* Used to: -Decrease use of endoscopic intervention -Discharge low risk patients earlier -Ensure rapid intervention in higher risk patients 2. Blatchford Score -Scaled at 0-23 with higher score = higher risk -Used to evaluate need for *urgent endoscopic intervention*

Generally precautions/counseling before starting a biologic

1. Screen for *TB in all patients* (TB skin test or alternative quantiferon-gold assay) 2. Screen for *Viral hepatitis (HBV and HCV) in ALL* 3. Can assess viral titers and liver enzymes Recommend vaccination or antiviral prophy as needed

Validated tools for Agitation Assessment

1. Sedation Agitation Scale (SAS) 2. Richmond Agitation Sedation Scale (RASS) - most common simple +4 to -5 scale between agitated and sedated

Septic shock

1. Sepsis + *vasopressor requirement* to maintain MAP > 65 2. Serum lactate level *> 2 mmol/L in absence of hypovolemia*

Big reasons you might use IV Ganciclovir

1. Severe *tissue invasion* 2. Severe *GI CMV infection* - can lead to poor absorption of -val and cause bad GI side effects

BBWs for ALL HepB Nucleoside Analogs

1. Severe acute exacerbations of hepB have been reported in patients discontinuing therapy for HepB. Monitor hepatic function closely with both clinical and lab follow up for at least *several months* in patients who DC therapy. Resuming may be warranted. 2. *Lactic acidosis* and *severe hepatomegaly with steatosis* (fatal in some cases) has been reported in using nucleoside analogues alone or in combination

What to do for treatment of acute *non-variceal GI bleed* in *patients who have ulcer with aflat, pigmented spots or clean bases seen on endoscopy*?

1. Start *STANDARD DOSE PPI* 2. Test for H. pylori AND eradicate if present

RA Basic Treatment Algorithm for *DMARD Naive*

1. Start with DMARD +/- short (3 mo) course of prednisone - MTX is gold 2. With moderate-high disease activity usually combine *DMARD or TNFi +/- MTX* OR a *Non-TNF biologic +/- MTX* orrrrr *Tolfacitinib +/- MTX* (Consider that xeljanz is only indicated after failure of 2 TNFis* *Single TNFi Inhibitor FAILURE* -Try non-TNF biologic +/- MTX or different TNFi +/- MTC -Usually try a different TNFi then if persistent go to Non-TNF or Xeljanz *Non-TNF biologic FAILURE* -Try another non-TNF biologic +/- -If still persistent try TNFi in TNF treatment naive (they shouldn't be) or Xeljanz +/- MTX

TCMR treatment options (3)

1. Steroid pulses 2. ATG 3. Increase maintenance immunosuppression

Treatment of T-cell mediated organ rejection

1. Steroid pulses. Usually IV methylprednisolone 250-1000 mg x 3 doses or high oral prednisone taper 2. ATG 3. Increase maintenance immunosuppression

Treatment of non-advanced (Stages I, II, or III) breast cancer

1. Surgery - Lumpectomy + RT - *always radiotherapy if NOT total mastectomy* OR -Total mastectomy +/- reconstruction -Assess lymph nodes w/sentinel lymph node dissection and axillary dissection 2. Radiation -Lumpectomy -Considered with mastectomy if there is lymph node involvement 3. Chemotherapy +/- targeted -Neoadjuvant to decrease tumor size and minimize surgery -Adjuvant with endocrine therapy, *ovarian ablation*, or chemo. Goal here is to cure the patient, prevent recurrence, and eradicate any residual undetected disease

Time of assessment to HBV treatment

1. Sustained (SR-6) = 6 months after DC of therapy 2. Sustained (SR-12) = 12 months after DC of therapy

LAM resistant treatment options

1. Switch to tenofovir and DC lamivudine 2. *ADD on* adefovir or entecavir. CONTINUED lamivudine

What are the 3 types of organ rejection?

1. T-cell mediated rejection (most common). Treat with high dose steroid or ATG 2. Antibody-mediated rejection (hyperacute or delayed onset). Treat with PP + IVIG 3. Chronic rejection (multifactorial, not just immune). Usually not reversible with current immunosuppression and *MAJOR cause of graft loss*

Endoscopic treatments for treatment of acute *non-variceal GI bleed*

1. Thermocoagulation 2. Argon plasma coagulation therapy 3. Injection sclerotherapy 4. Hemoclipping 5. Ligation

Additional IV vitamins that can be added to a TPN besides MVI

1. Thiamine 2. Folic acid 3. Ascorbic acid (vitamin C) -Vitamin K? (she doesnt have listed but you can)

Treatment "guideline" for sepsis

1. Treat infection w/in 1 hour (empiric abx) 2. Sepsis - abx + FLUID resuscitation 3. Septic shock - addition of vasopressors

Non-endoscopic tests to know for H. pylori

1. Urea Breath Test (UBT) - tests for *active H. pylori infection*. 95% sensitive and specific, results take around 2 days. Treatment with antibiotics, bismuth, PPIs, and H2RAs may cause *false-negative results*. Make sure to withhold PPIs or H2RAs for *2 weeks* and bismuth or antibiotics for *4 weeks* prior to testing. Always recommended *TEST TO CONFIRM ERADICTION posttreatment* 2. Fecal antigen test - Tests for ACTIVE H. pylori infection too. Sensitivity and specificity high like UBT for initial dx. Antibiotics, PPIs, and bismuth can also cause *false-negative results* but to a LESSER extent than the urea breath test. May be an *option in children*

Sulfsalazine contraindications

1. Urinary obstruction - can lead to nephrolithiasis and AKI - HYDRATE 2. Intestinal obstruction - leads to failure of enteric coated tablets and inadequate delivery of drug *Porphyria* - sulfonamides will *WORSEN* - not like HCQ where it treats paradoxically

Estimating energy expenditure

1. Use population estimates of cals per kg body weight 2. BEE (basal energy expenditure) Should use both to double check things

HepB Pathophysiology

1. Virion attaches to hepatocyte cell surface receptor and virus replicates 2. Liver damage as a result of immune mediated injury by *cytotoxic T cells* (NOT cytopathic unless very high viral load) leading to *increased LFTs*. This is an immune response to the *HBV core antigen* on hepatocyte cell surface. If cytotoxic T-cell response is weak, *chronic infection*

Subjective Global Assessment (SGA) areas

1. Weight change within *6 months* 2. Dietary intake 3. Presence of GI symptoms (anorexia, N/V, and diarrhea) 4. Functional capacity (activity level) 5. Disease state impact on metabolic demands

Favorable AML prognosis factors

1. Younger age! Huge if < 50 much better prog 2. Good performance status - you do an ECOG score (0 or 1 good, 2 moderate, 3+ frail) 3. Normal organ function 4. *Favorable cytogenetics* - t(8;21) = core binding factor or inv(16) or t(16;16) good

Total protein requirements in patients with cirrhosis

1.2-1.5 g/kg/day

Kcal/mL of different lipid percents (KNOW)

10% = 1.1. kcal/mL 20% = 2 kcal/mL 30% = 3 kcal/mL

Mucinous carcinoma

10% of tumors found Secrete *extracellular mucous*

% Daily calories from Amino acids

10-20% daily calories Done by weight: 0.8-2.5 g/kg/day

Caloric requirements for ill patients, metabolic stress, AND BMI *> 30*

11-14 kcal/kg ABW/day or 22-25 kcal/kg IBW/day

Capecitabine monotherapy adjuvant regimen

1250 mg/m2 PO BID *days 1-14 Q3wk* for *24 weeks*

What % of daily calories does IVFE provide

15-30% daily calories Done by weight - 0.5-0.75 g/kg/day

Normal BMI

18.5-24.9

Remicade onset time

2 weeks

Minimum lipid concentration given with TPN

20 g/L (2%)

Decitabine AML regimen

20 mg/m2 for *10 days (per slides - I am confused ask about this)* - repeat cycle every 4 weeks Note: Decitabine is *IV only* -= per my experience it can be given in outpatient infusion center over 1 hour for 5 consecutive days or inpatient for 3 days at 15 mg/m2 IV over 4 hours Q8H and response is often faster *2 cycles* slightly than azacitidine

IVFE and 20% and 30% potential advantages

20% and 30% contain *lower phospholipid to triglyceride ratio vs 10%* If TGs are high this comes into play

Caloric requirements for healthy patients

20-25 kcal/kg ABW/day

Sepsis will kill what percent of patients diagnosed?

25%

Overweight BMI

25-29.9

Caloric requirements for ill patients, metabolic stress, AND BMI < 30

25-30 kcal/kg (ABW)/day

Fluid resuscitation with crystalloid should be done within what time frame once hypo-perfusion is recognized?

3 hours

Score indicating pain with CPOT

3 or higher

Everolimus trough

3-6

CMV universal prophylaxis duration

3-6 months *900 mg x 200 days per IMPACT* Valganciclovir 450-900 mg QD or Ganciclovir 5 mg/kg IV QD

Onset of MTX effects in RA

3-6 weeks

What percent of calories should dextrose provide?

350 g/L (35%) central 100 g/L (10%) peripheral

Preferred Na range in TPN

40-100 mEq/L (Max 154 like NS)

What do you taper prednisone down to in kidney transplant?

5 mg *Steroid avoidance option for low low risk* -Careful due to increased rejection risk -Has been done

Score indicating pain with BPS

5 or higher

Sequential PUD treatment regimen (suggested not preferred)

5-7 days 1. PPI (std dose) BID 2. Amoxicillin 1 g BID THEN 5-7 days 1. PPI standard 2. Clarithromycin 500 mg BID 3. Nitroimidazole 500 mg BID

Onset for topical steroids in IBD

5-7 days for ALL

Aminosalicylates in IBD

5-ASA (mesalamine) is the active drug *DELAYED effect within 2-4 weeks* and response rate is only 40-80% If disease is ACTIVE is NOT as effective as corticosteroids

Sulfsalazine pharmacology

5-ASA and sulfapyridine components broken into by azoreductase Sulfasalazine is partially absorbed and excreted in bile - sulfapyridine is absorbed and *excreted in urine* 5-ASA is NOT absorbed and *excreted mainly in stool* So, most of the side effects come from the sulfapyridine and NOT 5-ASA. 5-ASA is also the active component

5-FU and LV MOA

5-FU activated in liver to *DHFR* active metabolite by *dihydropyrimidine dehydrogenase* Converted to *FdUMP intracellularly* which inhibits *thymidylate synthase* *Leucovorin increases amount of TS available* (prevents down-regulation)

What percent of patients in the ICU (all ICUs) experience moderate to severe untreated pain?

50%

% Daily calories from dextrose

50-60% total (150-350 g)

Standard induction chemo for AML

7 + 3 - the classic that has been done for years Cytarabine X 7 days at 100 mg/m2. This is a continuous infusion due to super short half life of cytarabine. Daunorubicin given at 60 or 90 mg/m2 IV bolus for 3 days

Hybrid PUD treatment regimen (suggested not preferred)

7 days 1. PPI (standard dose) 2. Amoxicillin 1 g BID THEN 7 days 1. PPI 2. Amoxicillin 3. Clarithromycin 500 mg BID 4. Nitroimidazole 500 mg BID

Maximum amino acid concentration in TPN

75 g/L (7.5%) - central 25 g/L peripheral

Azacitidine AML regimen

75 mg/m2 IV *or SQ* X 7 days every 4 weeks Note: SQ is preferred by some providers and it takes 2-4 cycles usually for response to be seen but may need 6. Most patients will be hospitalized for neutropenic ffever during this time.

Adenocarcinoma

90% of tumors in the large *intestine* *Grade 1* -Most differentiated, resemble adenomas *Grade 3* -Most undifferentiated, "high-grade" and worse prognosis

Underweight BMI

< 18.5

Caloric requirements for major burn injury (>50% total BSA)

> 30 kcal/kg ABW/day

Clinical presentation of breast cancer

> 90% of women present with a painless lump (solitary, unilateral, hard, irregular, nonmobile) -Around 80% of cases detected on breast self exam -Around 10% of patients complain of stabbing/aching pain as presenting sign Less common: Nipple discharge, retraction, skin dimpling

New ACCP/SCCM definition of Sepsis

>/= *2 point change in SOFA score* - measure of organ dysfunction SOFA = Sequential Related Organ Failure Assessment

ACR20 Definition (applicable to ACR50 and 70 too)

A composite measure defined as both improvement of 20% in the number of tender and number of swollen joints, and a 20% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [most often Health Assessment Questionnaire (HAQ)], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP).

The Non-Pharm Delirium ABCDEF Bundle

A: Assess, prevent, and manage pain B: Both spontaneous awakening and breathing trials (SATs and SBTs) C: Choice of Sedation D: Delirium: Assess, prevent, and manage E: Early mobility and *exercise* F: *Family* engagement and empowerment

What to do for treatment of acute *non-variceal GI bleed* in *patients who have ulcer with active bleeding, a non-bleeding visible vessel, or adherent clot*?

AFTER successful endoscopic hemostasis start *high dose IV PPI*

When to treat HBV for decompensated cirrhosis

ALWAYS TREAT

ALL vs AML Epidemiology

AML is most common in adults (especially elderly and male) ALL is most common in pediatric patients while AML is rarer. ALL is *the most common childhood malignancy*.

Neutropenia definition

ANC < *1 x 10^9* ANC is the percentage of WBCs that are neutrophils and bands

Ativan as an antieemetic

Acts as an anxiolytic, sedative, and amnesiac Ativan preferred due to intermediate half life. Works great for anticipatory vomiting - calms before chemo cycle

Nucleotide analogs for HBV

Adefovir Tenofovir AT Tide

DDIs with the CDK4/6 inhibitors

All should avoid use with concomitant CYP*3A4* inhibitor OR inducer. Can dose reduce if necessary with inhibitor Palbociclib is a weak 3A4 inhibitor and ribociclib is a moderate inhibitor

Options for induction immunosuppression

Always IV methylprednisolone intraoperatively *Options* 1. rATG (most common) 2. IL-2RB (basiliximab) 3. No antibody production

Humira biosimilars that are not on market

Amjevita Cyltezo Hyrimoz All for CD, UC, and RA

Nitrogen balance

Amount of Nitrogen Consumed -Amount of Nitrogen excreted in a given time frame Sepsis, burns, trauma, etc. results in increased protein breakdown and a *negative nitrogen balance - more is excreted than used to build*

Antibody present in Late acute, chronic, AND resolved HepB infection (just not seen in early acute phase)

Anti-HBcAg The core antigen is displated after virus infects hepatocytes and displays nucleocapsid protein - then this Ab is made. Indicates *active HBV replication*, which occurs later in acute phase. Expression of core antigen promotes immune-mediated cell death

Antibody present ONLY with resolved HepB infection (having had HepB)

Anti-HBeAg This is SEROCONVERTED from HBeAg - comparing allows us to *monitor response to treatment* WILL NOT HAVE WITH VACCINATION

Antibody present in resolved HepB infection OR vaccination

Anti-HBs Antibody to the surface antigen. Remember the surface antigen is what is used in the vaccine

Current HCV infection diagnostic findings

Anti-HCV (+) AND HCV RNA detected *Chronic infection if persistent HCV RNA > 6 months*

No current HCV infection diagnostic findings

Anti-HCV (+) AND *HCV RNA NOT detected*

Regulatory T cells

Antigen-specific CD4 T cells whose actions can *suppress immune responses* rather than stimulate *Two proposed mechanisms* 1. T cells compete for the same antigen 2. T cells compete for cytokine signals

Susbstance P/NK1 Receptor Antagonists on market

Aprepitant/fosaprepitant (Emend) -Available in many forms (IV is fos) -*STRONG CYP2C9 inducer* and substrate and moderate inhibitor of CYP3A4 Netupitant (Akynzeo) -Major CYP3A4 substrate Rolapitant (Varubi) -Substrate of 3A4 and moderate inhibitor of CYP2D6 -Not as much CYP interaction as other agents *Most increase dexamethasone conc 2-fold when co-administered*

H2RA Efficacy in ulcer prevention

At standard dose (QD) they are effective in reducing NSAID-related but NOT gastric ulcers At high dose (BID) may reduce BOTH duodenal and gastric ulcers but NOT as effective as PPI *NOT recommended as prophylactic cotherapy - PPI and misoprostol preferred* but could use for NSAID related dyspepsia

What to do in treatment failure for H. pylori PUD?

Avoid prior abx used and consider local antimicrobial resistance rates If FAILED bismuth quadruple - go to clarithromycin or levofloxacin contianing regimens If FAILED clarithromycin containing salvage - go to bismuth quadruple or levofloxacin containing salvage In treatment failure always *AVOID clarithromycin triple therapy*

What happens after ibrutinib is given

B cells are unable to proliferate and survive They think that BTK helps *"glue"* cells into the lymph system because after months of therapy cells go out into the blood and eventually die

Non-hodgkin lymphoma (90% of lymphomas)

B-cell lymphomas account for 85-90% T-cell and NK cell NH-lymphoma is uncommon, but highly aggressive with poor prognosis

Resting energy expenditure (REE) equation

BEE x stress factor

Dosing of PPIs and H2RAs for stress-ulcer prophy

BID dosing! e.g. Pepside 40 mg BID or pantoprazole 40 mg BID Once patient's OVERALL medical condition improves, *DISCONTINUE* prophylaxis

Place of lung cancer screening

Based off of National Lung Screening Trial -Looked at patieents CT vs CXR that smoked > 30 pack years and former smokers who quit in past 15 years Results: Screen *high risk patients (55-74 yo)* with *at least 30 ppy history* - could OVERDIAGNOSE indolent cancers by 18%

DLBCL (diffuse large B cell lymphoma) Staging

Based on number and location of lymph nodes involved *Above diaphragm only = stage 1 or 2* -Stage 1 only 1 lymph node involved -Stage 2 multiple involved *Above and Below diaphragm = stage 3 or 4* -Stage 3 = only 1 lymph node below involved -Stage 4 = > 1 lymph node involved below diaphragm. Many involved above and below.

Early Goal Directed Therapy (EGDT) basics in septic shock - ProCESS Trial

Basically decreased relative risk of in-hospital and 28D mortality AND death at 60 days Basically just made sure to *complete within 6 hours* all the goals of therapy (CVP > 8-12, MAP > 65, Urine output > 0.5 mL/kg/hr, and ScvO2 > 70%)

Premenopausal adjuvant endocrine therapy for breast cancer

Basically just *use tamoxifen* Aromatase inhibitor MONOtherapy is *contraindicated* -Can stimulate ovaries via increased GnRH release so won't work -HOWEVER, ovarian suppression with *LHRH agonist/antagonist with AI is acceptable and could be better with high risk of recurrence* *Options* -Tamoxifen -LHRH agonist () + AI -GnRH antagonist (leuprolide) + AI

ProCESS Trial

Basically looked at a decent patient population with *EGDT for Septic Shock* Protocol based resuscitation *DID NOT IMPROVE OUTCOMES*

When to do an esophagogastroduodenoscopy (EGD)?

Basically when any alarming symptoms are present (weight loss, GI bleed, worsening after NSAID avoidance and H2RA/PPI use) 1. If *evidence of ulcer or PUD bleed* on EGD, then biopsy of gastric mucosa is performed and tested for H. pylori 2. If *NO evidence* of activve bleeding on EGD with *no recent PPI/bismuth/antibiotic use* then biopsy urease testing is performed 3. If *No evidence* of active bleed on EGD with *recent PPI/bismuth/abx* use then *histology performed*. If negative, need follow up with urea breath or stool antigen to confirm negative

Adverse effects of hypomethylating agents

Better tolerated! -Myelosuppression -N/V -Diarrhea -*Mucositis* -*Fever* - neutropenic almost always happens -Fatigue

Propofol properties in sedation

Binds GABA, nicotinic, and muscarinic receptors Rapid on and off - useful for patients needing *frequent reawakenings* Dose dependent *resp depression AND hypotension* (must be on vent) - more in precedex *Toxicity* -Hypertriglyceridemia -PRIS

Midazolam MOA and properties for sedation

Binds GABAa receptor complex and lipophilicity allows for quicker penetration across BBB *The Good* -NO hypotension or bradycardia like propofol and dex -Shot onset and pretty short half life. Half life often > 4 hours though in critically ill (take long time for some patients to wake up) *The Bad* -Renally excreted, so can accumulate in renal dysfunction - Depresses the hypoxemic drive to ventilation + prolonged infusions can ppt withdrawal with abrupt DC - *MUST BE ON VENT* (like propofol continuous) -NO analgesic properties (like propofol) -*MOST associated with delirium* = major problem

mTOR inhibitor MOA

Block IL2 signalling downstream of receptor - inhibiting cell *proliferation*

General concerns with integrin inhibitors

Both nate and vedolizumab have *BBW for serious infections and malignancies* *General wa

How long can budesonide be used for crohn's and UC

Budesonide should only be used for *3 months with CD or 8 weeks with UC* - beyond this no clinical benefit

Why do you remove manganese in cholestasis?

Build up can cause neurotoicity

CRESTi Treatment Modalities for lung cancer

C = chemo R = radiation E = *NOT* endocrine therapy S = surgery T = targeted therapy I = Immunotherapy

Monitoring for 6-MP and AZA

CBC and LFTs biweekly for 3 months then every 3 months If after 2 weeks WBC is not < 4 and not decreased by > 50% baseline increase goal dose HOLD for WBC < 3.5 and recheck labs in 1 week. If consistent low, dose reduce In infection of significance HOLD until resolved May measure levels if no response in 3-4 months

Humira indications in IBD

CD - induction in maint - moderate-severe after conventional failed. Can *induce remission in those failing infliximab* UC - induction and maintenance same as above

Azathipprine and 6-MP indications

CD and UC *Maintenance ONLY* - for disease unresponsive to other std therapies or steroid dependent

Balsalazide (Colazal) site of action

COLON

Olsalazine site of action

COLON

Sulfsalazine site of action

COLON For CD or UC

Dexmedetomidine (Precedex) metabolism

CYP2A6 Caution with inhibitors like azoles

PPI clopidogrel drug interaction

CYP2C19 mediated! -Relevant for all PPIs except *pantoprazole* -Can decrease the antiplatelet effects -Conflicting evidence exists (COGENT study said its BS)

CapeOx

Capecitabine + Oxaliplatin Use adjuvant for high risk stage II or any stage III CRC

NSCLC "platinum doublet chemo" options

Cisplatin PLUS one of: -Vinorelbine -*Etoposide* -Gemcitabine -*Docetaxel* -*Pemetrexed* Carboplatin PLUS one of: -*Paclitaxel* -Gemcitabine -*Pemetrexed*

Backbone of chemotherapy NSCLC AND SCLC

Cisplatin or Carboplatin

SMART FLUIDS trial basics

Compared *NaCl vs balanced crystalloids (LR or Plasma Lyte-A)* *Results* -*Lower rate of composite death w/balanced crystalloids*, new RRT, and persistent renal dysfunction

Van Den Berge G trial (2001) for intensive insulin therapy in septic shock

Compared conventional (target BG of 180-200) to intensive insulin (Tarrget BG 80-110) *Overall Results* -Decrease in overall hospital mortality -Decreased sepsis 46% -Decreased polyneuropathy -Decreased ARF but....*more hypoglycemia with intensive vs conventional - 5.2 vs 0.8%* *Same guy 2006 trial* -Results NOT reproducible - NO significant reduction in mortality, but *ICE and Hospital LOS reduced*. In patients with LOS > 3 days hospital mortality was reduced -More hypoglycemia in intensive again

Prochlorperazine vs promethazine

Compazine generally preferred due to less sedation and side effects and better tolerability of IV infusion IV infusion of promethazine can cause phlebitis and burning during infusion

Hypertriglyceridemia prevention and treatment with PN

Concerned when TG > 400 mg/dL *Risk factors* -Preexisting problems, sepsis, etc. - IVFE infusion rate and dose *Treatment* -Decrease IVFE if TG > 400 and HOLD if > 1000 -If hypertriglyceridemia is due to pancreatitis DO NOT use lipids

Post-treatment testing for H. pylori

Confirmation is indicated in *ALL* patients *UBT or fecal antigen preferred* and should be obtained at least *4 weeks* post-treatment *Post treatment cure or eradication = NO organism detected 4 weeks after end of tx*

Ribavirin dosing in renal dysfunction

CrCL 30-50 mL/min: Alternate doses *200 mg one day and 400 mg other day* CrCl < 30 mL/min: *200 mg QD* HD: *200 mg QD*

Balsalazide (Colazal) indications

Crohn's AND UC - induction and maintenance of remission

Sulfsalazine indications

Crohn's AND UC for *induction* and maintenance of remission RA - induction and maintenance

Olsalazine indications

Crohn's AND UC induction and maintenance

UC and Crohn's Epidemiology

Crohn's is more common in *women* - slightly lower incidence Ulcerative colitis is *more common in men* Usually 1st peak occurs in *20-30s* then second peak occurrence in *60s-70s*

Cyclosporine DDIs with other immunosuppressants

CsA is a moderate CYP3A4 inhibitor, thus can increase levels of sirolimus or tacrolimus CsA also inhibits OATP

Cyclosporine - mycophenolate DDI

Cyclosporine inhibits OATP, so there is more in the blood that excretes via kidney. Lowers levels ultimately

Cytarabine pharmacology

Cytarabine is a pyrimidine antimetabolite pyrimidine analog *Admin* -If bolus called *HiDAC* (high dose arabinoside cytarabine) -For 7+3 it is given continuous for 7 days -For FLAG is given with fludarabine (and G-CSF) - fludarabine first for synergy *Metabolism* -INTRAcellularly metabolized to ara*cytidine*-triphosphate (ara-CTP) by *deoxycytidine kinase* (rate limiting step* -Has a VERY short half life (7-20 minutes) hence given continous -Most (80%) is metabolized to *uracil arabinoside (ARA-U)*, by *cytidine deaminase* which is *NOT active* AND *is TOXIC*

Moderate risk serostatus for CMV

D+/R+ Somewhat protective because patient already has antibodies against CMV

High risk serostatus for CMV

D+/R- Most likely to develop primary infection and have most symptoms/damage *Also high risk* -Anti-thymocyte globulins

Lowest risk serostatus for CMV

D-/R- Must be transmitted through body fluids or tissue, so at relatively low risk

Topo II Inhibitors for AML

Daunorubicin (most common), idarubicin, and mitoxantrone *Mechanisms* -Topo II inhibition = ds break -Intercalate in DNA as well *PK* -Can give as bolus due to 24-30 hr half life, which is why dauno QD X 3 days for 7_+ 3 -Hepatic metabolism Note: anthracycline exposure is also one of the biggest risk factors for sAML Counseling: they are red in color

ARISE Trial for Goal-directed resuscitation for patients with early septic shock

Decent # of patients - *EGDT vs usual care* *EGDT did NOT decrease 90 day all cause mortality*

Substance P and NK1 inhibitors have substantial effects on _______________

Delayed N/V in particular

How long do you need to wait before initiating a PN?

Depends on patient *age and clinical status* -In previously well-nourished, clinically stable adults meeting PN criteria, consider starting after 7-14 days of subobtimal nutrition intake

VASST (Vasopressin and Septic Shock Trial)

Designed to evaluate mortality benefit when comparing use of open label vasopressors plus either NE or low dose vasopressin in septic shock *Results* -Decreased mortality *WITH CORTICOSTEROID* USE in vasopressin group vs NE group at 35.9% vs 44.7% -Better 28D mortality in pts on vasopressin with less severe septic shock

DAI Macronutrient Caloric densities

Dextrose = 3.4 kcal/gram - *50-60% total daily calories* Amino acids = 4 kcal/gram - *10-20% of total daily calories (can exceed)* IVFE = 10 kcal/gram - *15-30% of daily calories*

Delzicol vs Asacol HD forms of mesalamine

Different doses but BID or TID for delzicol NOT interchangable

Crohn's disease common locations

Distal ileum = Right colon (35%) > Colon (20%) Also possible in gastroduodenal (where SI starts) or in small intestine In general proximal colon and distal ileum most common

Mycophenolate drug-drug interactions

Drugs can interfere with *MPAG/MPA enterohepatic recirculation* and *decrease MPA AUC* -Alum/Mag containing antacids -Cholestyramine -Sevelamer -Recommend separating by at least 2 hours

HepB vaccines for kids

Energix Reombivax

HBV treatment naive 1st line for compensated or decompensated cirrhosis

Entecavir

Velpatasvir/Sofosbuvir

Epclusa

HepC drugs available as generic

Epclusa Harvoni

HepC drugs with Pan-genotypic *GT1-6 activity*

Epclusa (velpatasvir - NS5Ai and sofosbuvir - NS5Bi) Vosevi (sofosbuvir - NS5Bi and voxilaprevir - NS3/4A protease i) Mavyret (glecaprevir - NS3/4A protease i and pibrentasvir - NS5A inhibitor)

Basal Energy Expenditure (BEE)

Equation used to estimate energy expenditure Advantage: Incorporates patient's age, height, weight, gender, and clinical condition

Genetics and DLBCL outcomes

Essentially, the more subtypes (ABC, GCB etc) or mutations a person has in lymphoma cells, the worse the outcomes *"Double hit" DLBCL* has the worst outcomes with median overall survival of 30 months,. This means there is a *MYC gene and BCL2* gene rearrangement. Esentially both *MYC and BCL2 are overexpressed*

How often should you see patients and assess RA treatment

Every *3 months* Treat to target strategy for low disease activity

Epclusa (velpatasvir/sofosbuvir) indications and admin

FDC 1 tablet once daily for *GT1-6 - PANgenotypic*

Vosevi (sofosbuvir/velpatasvir/voxilaprevir) indications and admin

FDC 1 tablet once daily for *GT1-6 - PANgenotypic*

Harvoni (sofosbuvir/ledipasvir) indications and admin

FDC 1 tablet once daily for *GT1/4*

*Intensive* stage IV CRC options

FOLFOX +/- bevacizumab, cetuximab, or paitumumab FOLFIRI +/- bevacizumab, cetuximab, or paitumumab FOLFOXIRI +/- bevacizumab Capecitabine +/- oxaliplatin and/or bevacizumab

Regulatory T cells contain this marker protein

FOXP3

Sulfsalazine onset

Faster than HCQ but slower than MTX

Steroids in IBD

First line for induction of remission - ACUTE ONLY *1/3 of pts become steroid dependent and 20% lose response to steroids after 1 year*

Treatment for patients deemed *at risk* (NOT active) of NSAID related ulcer

First line is PPI (preferred) or misoprostol Must weigh the NSAID-related *GI bleed risk and CV event risk* when recommending -Eradicate H. pylori if present *Cotherapy depends on risk assessment!*

Idiopathic GI bleed treatment

Follow initial treatment approach with high dose PPI (IV) for active bleed X 72 hours then continued After initial treatment start *standard dose* PPI 40 mg *TWICE DAILY* for *14 days* (same as NSAID!) followed by standard dose 40 mg *ONCE DAILY* Long-term

Complete response to HBV treatment definition

Fulfill criteria of biochemical + virological response + loss of HBsAG *Biochemical* -Decreased serum ALT to within normal range *Virological* -Undetectable serum HBV -Loss of HBeAg (seroconversion) in persons HbeAg+

Zepatier (elbasvir/grazoprevir) genotype activity

GT1 GT4

Harvoni (ledipasvir/sofosbuvir) genotype activity

GT1 GT4 GT5 GT6 1,4,5,6

Guideline recommendations for BG in septic shock

Generally, multicenter trial suggest no mortality benefit and higher rates of hypoglycemia and adverse events with tight glycemic control *Overall recommendations* 1. Protocolize BG control 2. Insulin initiated with 2 BG readings > 180 mg/dL and target BG *< 180* 3. ALL patients receiving IV insulin therapy should receive a glucose CALORIE SOURCE and be monitor every 1-2H until glucose and insulin infusion rates stable then every 4 hours

Day *2-4* Prophylaxis for MODERATE emetogenic risk chemo

Give prophy on days *2-3* (note 2-4 in HIGH risk) 1. If no NK1 on day 1, 5-HT3 antagonist monotherapy days 2-3 or dexamethasone monotherapy days 2-3 2. If aprepitant on day 1, then aprepitant days 2-3 +/- dexamethasone days 2-3 3. If fosaprepitant, rolapitant, or NK1/5-HT3 antagonist on day 1, then +/- dexamethasone days 2-3 4. If olanzapine used day 1, olanazapine ONLY days 2-3

Day *2-4* Prophylaxis for HIGH emetogenic risk chemo

Give prophy on days *2-4* 1. If aprepitant used day 1 then also on 2-3 PLUS dexamethasone days 2-4 2. If fosaprepitant or rolapitant on day 1, then dexamethasone on days 2-4 3. If olanzapine used day 1, then alanzapine ONLY days *2-4* Note: Dexamethasone always day 1

Morphine metabolism

Glucuronidation to active metabolite glucose-6-glucuronide which is 20-40X more potent than parent drug

Vomiting Grading

Grade 1: 1-2 episodes (separated by 5 min) in 24 hours Grade 2: 3-5 episodes (separated by 5 min) in 24 hours Grade 3 (severe): >/= 6 episodes in 24 hours. Need of tube feeding, TPN, or *hospitalization* Grade 4 (life threatening): Urgent interventions are indicated, dangerous Grade 5: Death

Grading of Vomiting in cancer

Grade 1: 1-2 episodes in 24 hours Grade 2: 3-5 episodes in 24 hours Grade 3: 6 or more episodes in 24 hours, tube feeding, TPN, or hospitalization Grade 4: Life threatening consequences and urgent care needed Grade 5: Death

Nausea Grading

Grade 1: Loss of appetite without alteration of eating habits Grade 2: Oral intake decreased without significant weight loss, dehydration, or malnutrition Grade 3: Inadequate oral caloric or fluid intake (*malnutrition*), tube feeding, TPN, need *hospitalization* No grade 3 (life threatening) or 4 (death) from nausea alone

Most common bacterial class and location in sepsis

Gram positives - Respiratory tract infections

Myeloblasts can differentiate into

Granulocytes and Monocytes *Granulocytes* 1. Basophils 2. Neutrophils 3. Eosinophils *Monocytes* -Precursors to macrophages

NS3/NS*5A* protease inhibitor (Second generation)

Grazoprevir (NS3 protease) + Elbasvir (NS5A inhibitor) Zepatier

JAK inhibitor place in therapy for RA

Gudelines usually say *try 2 TNFi's first AND 2 non-TNFi's* before a JAK inhibitor Tolfacitinib (Xeljanz) Barictinib (Olumiant)

HBV Treatment in Compensated Cirrhosis for HBeAg+ and -

HBV DNA > 2,000 OR ALT > 2X ULN

When to treat HBV for non-cirrhotic patients if HBeAg -

HBV DNA > 2,000 or 20,000 AND ALT > 2X ULN

HepB antigen only present in LATE ACUTE and possibly chronic HepB infection

HBeAg HepB e antigen Seen during ACTIVE HBV replication - this is the one replaced by anti-HBeAg once infection is resolved

Early Phase AND late phase HBV Antigen for both acute and chronic HepB

HBsAg HepB surface antigen

If *immune to Hep B by vaccination* you will see these results

HBsAg = Negative (this is only with infection) anti-HBc = Negative (would have to have had actual infection - response to viral capsid protein) anti-HBs = POSITIVE (indicated protection)

If *acutely infected with HBV* you will see these results

HBsAg = Positive anti-HBc = Positive IgM anti-HBc = Positive anti-HBs = Negative (not until recovery - grants immunity)

If *chronically infected with HBV* you will see these results

HBsAg = positive anti-HBc = positive IgM anti-HBc = Negative (now > 6 months this is gone) anti-HBs = Negative (only positive if immune and infection resolved)

CO equation

HR x SV

Ledipasvir/Sofosbuvir

Harvoni

Most common chronic hepatitis

Hep C

anti-HBs

Hepatitis B surface antibody (+) = protected -Present at recovery and immunity from HBV infection -Successful vaccination - valid if performed 1-2 months post 3rd dose

HepB vaccine for adults ONLY (18+)

Heplisav-B

Liver transplant recommendation at UM

Higher risk of infectious complication Tacro, mycophenolate, and prednisone recommendation *Wean off mycophenolate and prednisone* due to infection risk

TPMT genetics with Aza or 6-MP

Homozygous recessive or low to absent activity (0.8%) = Consider alternatve Intermediate activity or heterozygous variant (11%) = start at *50% of starting dose and titrate by 2 wk intervals to goal dose* Normal to high activity (89%) = Start normal dose and titrate to goal in 2 week intervals

CORTICUS Study (2008) on steroids in septic shock

Hydrocortisone IV ONLY (high dose 50 mg X 5 days then tapered) *Results* -NO mortality benefit -Faster resolution of septic shock in those getting steroids

APROCCHSS (2018) study for steeroids in septic shock

Hydrocortisone IV PLUS Fludrocortisone *90D mortality lower in steroid group*

Annane study (2002) on steroids in septic shock

Hydrocortisone PLUS fludrocortisone *reduced 28D mortality and duration of vasopressor*

Cortifoam form and site

Hydrocortisone foam -Rectum and descending colon

Albumin vs prealbumin in nutrition (starred)

Hypoalbuminemia can indicate malnutrition, however both albumin are negative acute phase proteins and *NOT sensitive or specific indicators of nutritional status* *Prealbumin* -Has SHORTER HALF LIFE, so may be better marker to *evaluate response to nutrition support* than albumin. Measure once weekly

Hallmark sign of refeeding syndrome

Hypophosphatemia

Treatment duration for HBV therapy

IFN based = predefined duration *NAs given until specific endpoint achieved* -HBeAg (+) - treat until seroconversion AND HBV DNA undetectable *+ additional 6 months* -HbeAg (-) - treat until HBsAg clearance

Ixekizumab (Taltz)

IL-17 inhibitor *Side effects* -URTIs, oral candidiasis -Monitor for onset OR exacerbation of *inflammatory bowel disease* - can also happen with Crohn's and ulcerative colitis NOTE: IL-17 is important in the gut!

Eosinophillic allergic reactions are primarily driven by ___________

IL-5

Anakinra (Kineret)

IL1 Receptor Antagonist *Uses* -RA -Cryopyrin-associated periodic syndromes (CAPS) *Benefits* -Lower risk of infection compared to other IL-antagonists

Anakinra (Kineret)

IL1 Receptor Antagonist Indicated for NOMID, RA, gout, etc. (inflammation) *Uses* -RA -Cryopyrin-associated periodic syndromes (CAPS) *Benefits* -*Lower risk of infection* compared to other IL-antagonists

Valganciclovir prophy dosing based on renal dysfunction

If CrCL > 60 always do 900 mg QD If CrCl 40-59 only do you do 450 mg QD

Aspirin in NSAID induced GI bleeding

If on aspirin for primary CV prevention *DO NOT RESUME* and *Continue long term PPI* For patients on aspirin for secondary CV prevention with GI bleed: *Restart low-dose aspirin ASAP* when GI bleed stops - ideally *within 1-3 days but up to 7 days* after bleeding stops -Must add *long term PPI with aspirin*

Simponi (golimumab) indications in RA

In *combination with MTX* for moderate-severe active disease

Nuclear Factor kB (NF-kB)

In activated B Cell-like (*ABC*) DLBCL, receptors are overexpressed and lead to *overstimulation of NF-kB* -NF-kB can result in overexpression of MYC (transcription regulator - more = more proliferation) or BCL2 (anti-apoptotic) NF-kB is specific to ABC NOT GCB

Clinically *specific* PUD symptoms

Include general synmptoms (N/V, dyspepsia, etc) PLUS *epigastric abdominal pain radiating to the back*

Trace element increase for patients with poor wound healing (e.g. burns)

Increase Zinc in TPN

Zepatier clinically significant side effect

Increased ALT levels CI in Child-Pugh B or C

HBV DNA

Increased levels = infectious -Viral replication-incubation occurs in 1-6 months -100K to 1 billion copies per mL - baby replicates fast -Level *< 300 copies/mL = inactive infection* Used to *MONITOR TREATMENT EFFECTIVENESS*

When to expect signs and symptoms of acute HAV after infection

Incubation period on average 28 days Viremia within *1-2 weeks of exposure* *Symtpoms* -Preicteric phase - abrupt and nonspecific -Icteric phase - worsening systemic symptoms (> 28 days) -LFTs increase *within first weeks of exposure and peak at ~4 weeks* No chronic infection, rarely complications

Sulfsalazine indications in RA

Induction AND maintenance therapy Onset at least 4 weeks

Calcineurin inhibitors work for immunosuppression by ________

Inhibition of the *IL-2 production* pathway

irAE Basic Management

Initial = steroids PO or IV solu-medrol -When sx improve to grade 1 taper over at least *4-6 months* -Give *PCP prophylaxis* for prolonged immunoqsuppression *Refractory irAEs* -Alternate immunosuppressant like *infliximab, cellcept, or tacrolime

Belatacept can be used in ______ transplant

Kidney

EGFR *ACTIVATING* mutation positive NSCLC 1st line targeted therapy (only locally advanced or metastatic)

Know *Osimertinib (Tagrisso) 80 mg PO QD* Others -Erlotinib (Tarceva) -Afatinib (Gilotrif) -Gefitinib (Iressa) -Dacometinib (Vizimpro)

Dopamine PD

LOW doses (< 5 mcg/kg/min): Activates *dopaminergic* receptors and vasodilates renal and mesenteric beds MODERATE doses (5-10 mcg/kg/min): Activates *B1 receptors*. Positive inotrope and chronotrope HIGH doses (>10 mcg/kg/min): Activates *alpha 1 receptors* causing *vasoconstriction* *PROBLEM: Higher risk of arrhythmias*

Branced chain amino acids

Leucine Isoleucine Valine KNOW: *Thought to NOT cross BBB*

NICE SUGAR Trial (2009)

Looked at "intensive" BG control at 81-108 vs conventional < 180 mg/dL *Increased mortality in intensive group vs conventional* - Hence we use a < 180 goal now

Dopamine vs NE big trial

Looked at 1700 patients requiring vasopressor for shock treatment *Similar results, BUT significantly higher rate of arrhythmia in dopamine group - hence we now use NE first line*

ADRENAL (2018) study for steroids in septic shock

Looked at Hydrocortisone IV inf X 7 days vs placebo DID NOT reduce 90 day mortality

ATHOS 3 Trial

Looked at patients receiving NE with placebo or *angiotensin II* for septic shock *Results* -ANGII increased BP in those that didnt respond to other high dose vasopressors, BUT *higher thromboembolic events*

Highest risk transplants for CMV

Lung, small bowel > heart and pancreas > kidney and liver

How is CMV infection detected?

MAIN: Quantitative CMV-*PCR* Other less sensitive: -pp65 antigenemia -Tissue or shell via culture

MAP goal in septic shock

MAP >/= 65 mm Hg

TPN administration filters

MUST administer all through IV infusion pump If AA-Dex (no IVFE), admin through *0.22 micron filter* If 3 in 1 (coinfusion w/IVFE), use *1.2 micron filter* due to 0.5 micron lipid particles The filters remove particulate, air, and microorganisms

Ulcerative colitis anatomic distribution

Mainly in the *rectum (proctitis) or colon* Left sided colitis only possible Pancolitis (across colon) also common Form unique *crypt abscesses*

6-Mercaptopurine dosing

Maintenance ONLY Start at 0.75 mg/kg/day and titrate to *GOAL 1.5 mg/kg/day* increasing at 2wk intervals May need to start lower dose depending on TPMT genetics. Start at normal dose if *TPMT high activity*

Azathioprine dosing

Maintenance med ONLY Start 1 mg/kg/day then titrate to GOAL of 2.5 mg/kg/day *increasing at 2 week intervals* May need to start at lower dose depending on *TPMT genetic polymorphism* AND/OR level - if *HIGH activity (89% of people) start at normal dose*

Glecaprevir/pibrentasvir

Mavyret

Min and max dextrose concentration in TPN

Max: 35% (350 g/L) - just divide grams my TPN mL to check Min: 10% For peripheral lines max dex concentration is 10%

Min and max protein concentrations

Max: 75 g/L (7.5%) Min: 40 g/L (4%)

If a patient has AML with identified *FLT3 mutation*, what can you add to standard induction (more likely consolidation) regimen?

Midostaurin Midaustaurin is actually a tyrosine kinase inhibitor that inhibits multiple kinases including FLT3 WT and mutant. Inhibiting FLT3 signalling stops signalling of proliferation and induces apoptosis in leukemic cells

Enbrel indications

Moderate-severe active RA *with or without MTX

Macrophages are mature _________

Monocytes

Everolimus Pearls

Most common by fare vs Sirolimus CNI sparing regimen *Kidney* -Increased risk of nephrotoxicity if used with standard dose CsA - reduce CsA dose/trough goal -Low-dose CNI + ERL was noninferior to std dose CNI + MMF in trial *Liver* -Low dose TAC + ERL vs standard dose TAC - better renal function with comparable loss/death, but higher rate of drug DC

Cyclosporine DDIs with other immunosuppressants

Must INCREASE mycophenolate dose with CsA Must DECREASE everolimus or sirolimus with CsA

Entecavir administration

Must be given on an empty stomach

M - staging for CRC

Mx - cannot assess M0 - no metastasis M1 - distant metastasis

CellCept vs Myfortic

Myfortic is the EC delayed release formuation, but ended up having the *same side effects and everything else*

Should you use steroids for maintenance treatment of UC and Crohns?

NEVER - not indicated and should always taper and DC

Ketamine MOA and properties in sedation

NMDA antagonist *The Good* -Has BOTH analgesic and sedative properties -Actually *increases BP* which could be useful in shock (decreasing vasopressor requirement) -Does NOT reduce respiratory drive (similar to Dex* *The Bad* -Unsure if contributes to delirium development -Not a ton of experience and data for use - emerging now

Azathioprine and 6-MC site and onset

NON-SPECIFIC Take at least *3 months to work*

Carboplatin special dosing

NOT dosed by mg/m2 like most things but rather by the *Calvert equation* which uses AUC target and CrCl to calculate the dose

Grazoprevir (GZR) class

NS3 protease inhibitor

Voxilaprevir (VEL) class

NS3/4A protease inhibitor (like glecaprevir and grazoprevir)

-Previr class

NS3/4A protease inhibitors

Elbasvir (EBR) class

NS5A inhibitor

Velpatasvir (VEL) class

NS5A inhibitor

-Asvir class

NS5A inhibitor -Elbasvir (in Zepatier) -Ledipasvir (in Harvoni) -Velpatasvir (in Epclusa)

Ledipasvir (LDV) class

NS5A inhibitor (like velpatasvir)

Sofosbuvir class

NS5B polymerase inhibitor

Preferred NSAID for CV safety

Naproxen

PD-1 (receptor) inhibitors

Nivolumab (Opdivo) Pembrolizumab (Keytruda)

Substance P/NK1 receptor antagonist adverse effects

Not many: generally well tolerated -Headache -Dizziness -Fatigue -GI -Hiccups

Calvert equation for Carboplatin dosing

Note: GFR is calculated using Cockroft Gault, but the *dosing weight and rounding of SCr is variable* and provider dependent

Trastuzumab side effects

Note: Generally well tolerated clinically *High incidence* -Pain -Asthenia -Fever and chills -Nausea/vomiting -HA -Diarrhea -Abdominal pain -Back pain -Infection *Less frequent* -Anorexia -Flu syndrome -Tachycardia -CHF

Adefovir vs Tenofovir

NucleoTIDE analogs -Tenofovir is similar in potency to adefovir but *less nephrotoxic* and *ACTIVE in HIV* -Vs. adefovir in HBeAG (+) there were more patients with undetectable HBV DNA, HBeAg seroconversion, and ALT normalization

LAM resistant HBV antivirals

Nucleoside -Entecavir Nucleotide (both) -Adefovir (WT and LAM resistant) -Tenofovir (both types)

HBV antivirals approved for decompensated cirrhosis

Nucleoside analogs 1. Lamivudine 2. Telbivudine 3. Entecavir Nucleotide 1. Tenofovir *disproxil fumarate* (alafenamide is compensated ONLY)

Renal AND hepatically eliminated HBV antivirals

Nucleotide analogs 1. Adefovir 2. Tenofovir *alafenamide*

N-staging for CRC

Nx - regional lymph nodes cannot be assessed N0 - no regional lymph node metastases N1 - metastasis in *1-3 pericolic or perirectal* lymph nodes N2 - metastasis in *4 or more* pericolic or perirectal lymph nodes N3 - metastasis in any lymph nodes along course of *vascular trunk*

Tolfacitinib (Xeljanz) IBD indication

ONLY for *UC* - moderate to severe disease after inadequate response or intolerance to TNFi (off label!)

Dobutamine place in therapy for septic shock

ONLY for *persistent hypoperfusion* despite adequate fluid loading use of vasopressin agents

Pouchitis development

Occurs from idiopathic inflammation after ileal pouch anal anastomosis (IPAA) procedure Recommended to use *short course of metronidazole or ciprofloxacin*

Consequences of delirium

Occurs in 50-80% of ICU patients *Associations* -Increased mortality -Prolonged ICU and hospital LOS -Development of post-ICU cognitive impairment -Placement in SNFs -Increases health care eexpenditures

Serotonin antagonists

Ondansetron: major substrate of CYP3A4 Granisetron (Kytril) - nothing cool Palonosetron (Aloxi or Akynzeo with netupitant) - *NOT QT prolonging*

PARP inhibitors for recurrent or metastatic BC

Only for *HER2 NEGATIVE and BRCA1/2 mutations* -Olaparib (Lynparza) -Talazoparib (Talzenna)

When do you automatically use targeted therapies for NSCLC

Only in *Stage IV* *No known mutations* -If PD-L1 expression is > 50% use Keytruda *MONOTHERAPY* -If PD-L1 expression < 50% can use immunotherapy + chemo or chemo alone *Known Mutations* -*ALK = Alectinib (Alecensa) preferred* or brigatinib (Alunbrig), certitinib (Zykadia), or crizotinib (Xalkori) -*EGFR mutation = Osimertinib (Tagrisso!)* preferred, erlotinib (Tarceva), gefitinib, or dacomitinib options -*ROSI mutation = Crizotinib (Xalkori) or entrecitinib (Rozlytrek) preferred*, or ceritinib -*BRAF mutation = Dabrafenib (Tafinlar) + Trametinib (Mekinist) prefered (Combo drug)*, vemurafenib (Zelboraf) OR chemo/immunotherapy options -*NTRK gene fusion = Larotrecitinib (Vitrakvi) or Entrecitinib (Rozyltrek) preferred* or chemo+immunotherapy option

HBV Treatment in Non-cirrhotic Patients for HBeAg+

Only treat if: HBV DNA > *20,000* AND *ALT > 2X ULN* If ALT < 2X ULN just observe

Standard dose PPI therapy

Oral PPI once or twice daily (or IV bolus if needed) -Twice daily in specific patients: NSAID induced

Corticosteroid formulation choice

Oral prednisone more for middle involvement and has *dose-response effect* (20-60 mg/day). Increased dose also means more side effects though. Budesonide and rectal forms only affect local areas Topical corticosteroids are effective in ACUTE treatment of distal colitis (UC) but NOT proven in maintaining remission Budesonide should only be used for *3 months with CD or 8 weeks with UC* - beyond this no clinical benefit

EGFR TKI sensitivity (Lung Cancer)

Overall 10% of caucasians and *50% asians* with *EGFR sensitizing mutation* -Exon 19 del, Exon 21 sub, exon 18 *TKI resistance = exon-20 insertion*

Epclusa (sofosbuvir/velpatasvir) genotype activity

Pan-genotypic (G1-6)

Glecaprevir/Pibrentasvir (Mavyret) genotype activity

Pan-genotypic (GT1-6)

Vosevi (sofosbuvir, velpatasvir, and voxilaprevir) genotype activity

Pan-genotypic (GT1-6)

Sofosbuvir genotype indication

Pan-genotypic, BUT *combining with other agents limits activity*

IV lorazepam excipient concern

Parenteral formulation contains *propylene glycol* as diluent *Toxicity* -Usually with exposure to HIGH DOSES for LONG periods -Manifests as *anion gap metabolic acidosis* AND *AKI* Monitor: Osmol gap, renal function

Benzodiazapines for agitation/sedation general

Potency of lorazepam > midazolam > diazepam ALL metabolized by *liver* and elderly are *more sensitive* Can and DO cause respiratory depression (must be on vent) and systemic hypotension (less of concern)

Induction phase of immunosuppression

Pre-op through early post-op Involves *high dose corticosteroids* and often utilize antibody induction with *ATG or basiliximab* - basicliximab only if at lower immunologic risk Also *need infection prophylaxis* for 1-6 months after transplant when on maintenance immunosuppressants

Leflunamide contraindications and BBWs

Preg cat X AVOID in lactation *ADRs* -Hepatotoxicity - usually asymptomatic transaminitis, but can be severe and fatal - linked to *CYP2C9 poor metabolizer* phenotype -Bone marrow suppression - *pancytopenia, thromobocytopenia, agranulocytosis* - usually more with concomitant MTX

Allogeneic stem cell transplant for AML

Prognosis: 40-60% EFS > 3 years after transplant - this is the *ONLY way to achieve possible cure* *Positives* -Lower risk of relapse than chemo (9-35% if done after/within first remission) *Negatives and risk* -30-45% treatment related mortality due to *opportunistic infections, chemo induced organ damage, and GVHD* Note: They have to kill virtually all bone marrow cells before transplant which requires some hefty chemo and/or radiation. GVHD is relatively common.

Hep B Immunoglobulin

Provides temporary passive immunity *post-exposue* to HBV - uncommon to use

Enteral nutrition (EN)

Provision of nutrients through the gastrointestinal tract when the client cannot ingest, chew, or swallow food but can digest and absorb nutrients. Give through tube in patients who *cannot eat AND have functional and accessible GIT*

Preload measurement

Pulmonary capillary wedge pressure

Double hit DLBCL treatment

R-DA-EPOCH Rituximab Etoposide Prednisone Vincristine (Oncovin) Cyclophosphamide -Doxorubicin (Hydroxydaunorubicin) Basically R-CHOP with etoposide -Consider CNS prophylaxis -Consolidate with *autologous (from yourself) transplant*

Double hit DLBCL treatment - *GCB ONLY!!*

R-DA-EPOCH Rituximab Etoposide Prednisone Vincristine (Oncovin) Cyclophosphamide -Doxorubicin (Hydroxydaunorubicin) Basically R-CHOP with etoposide -Consider CNS prophylaxis -Consolidate with *autologous (from yourself) transplant*

Baricitinib (Olumiant) indications

RA after *failing TNFi* Recommended per guidelines after failing *2 TNFi and 2 N-TNFis* JAK inhibitor

Methotrexate indications

RA only

Agitation scoring tool and goals

RASS - Goal is to keep in 0 to -2 range *-1: Drowsy - not fully alert, but sustained awakening. Eye opening and eye contact to voice for > 10 seconds* *-2: Light sedation - briefly awakens with eye contact to voice but < 10 SECONDS*

Refeeding syndrome prevention and treatment

RS usually occurs in first 3-5 days of nutrition therapy and the hallmark sign is *hyperphosphatemia* *Prevention* -Correct electrolyte abnormalities BEFORE starting TPN -Add *thiamine 100 mg QD for 5-7 days* -AVOID overfeeding - start low and slow *Treatment* -Depends on severity and time course -*STOP nutrition therapy* -Aggressive supplementation of electrolytes - K, Mg and Phos based on serum levels

Sodium requirements in TPN

Range 40-100 mEq/L Remember to multiply NaPhos *by 1.33 for Na calc* *Max = 154 MeQ/l - SAME as NS*

Diazepam for agitation

Really not good at all super long half life due to active metabolite Metabolized by CYP3A4 Accumulates due to lipophilicity and active metabolites

HBV vaccines for immune suppressed or HD patients > 20 yo

Recombivax HB *X 3* @ 0,1, and 6 months Energix-B *X 4* @ 0,1,2, and 6 months Heplisav-B *X 2* @ 0 and 1 month

Canasa site of action

Rectum *Only in suppository*

MTX onset time

Relatively fast *3-6 weeks*

Biologics only indicated for RA in COMBO with MTX

Remicade Golimumab (Simponi)

Stage IIIA NSCLC treatment options

Resectable: neoadjuvant chemo, surgery, or adjuvant chemo Unresecctable: radiation, chemoradiation, immunotherapy with *durvalumab (Imfinzi)* Clinical trial always an option

Gancicyclovir resistance management

Resistance can arise with prolonged underdosing of VGCV or GCV *UL97 or UL54* mutations associated *Alternatives* -High dose 10 mg/kg IV Q12H GCV -Cidofovir (UL54 crss-resistance seen) -Foscarnet -CMV IVIG -Letermovir Note: *Cidofovir and Foscarnet are VERY NEPHROTOXIC*

Crohn's disease activity index (CDAI) basics

Response = *> 70 point decrease in CDAI score* -Remission if score < 150 Max score is 600

Dose related toxicity with hydroxychloroquine

Retinopathy At doses > *600 mg*

Leflunimide overall mechanisms

Reversible dihydroorotate dehydrogenase inhibitor Stops de novo pyrimidine synthesis Decreases T-cell proliferation ultimately

PRIS S/S and Risk factors

Risk at > 80 mcg/kg/min for > 48 hours *S/S* -Worsening *metabolic acidosis* -Hypotension with inc vasopressor req -Arrhythmias -AKI -*Hyperkalemia* -*Rhabdomyolysis* -Liver dysfunction

TDM for immunosuppressants

Routine for CsA, TAC, SRL, and ERL - narrow TI -Initial dose based on weight or fixed dose -Whole blood concentration prior to morning dose by LC/MS/MS *Therapeutic range is individualized* - organ specific, time post-transplant, concomitant immunosuppression, rejection/infection history, side effects

Baricitinib BBW

Serious infections and malignancy *Thrombosis* - DVT, PE, and arterial thrombosis

Tolfacitinib BBW

Serious infections and malignancy (same as TNFi)

CDAI Scoring of CD

Severe/fulminant if > 450 Moderate-severe if 220-450 Mild-moderate if 150-219 In remission if < 150

Dextrose max infusion rate (KNOW)

Should *NOT exceed 4-7 mg/kg/min for adults* *If too high* -Increased O2 consumption and CO22 production -Increased energy expenditure -Hyperglycemia -Increased levels of bc markers indicating fatty infilatration of liver

Telbivudine for HBV

Similar structure to LAM, but *NOT active in HIV* *Advantages* -Can be used in compensated *AND* decompensated -*MOST POTENT* vs LAM in decreasing *HBV DNA and normal ALT levels* *Disadvantages* -Higher resistance rates in HBeAg (+) and HBeAg (-) -Telbivudine resistant mutations are *cross-resistant with LAM* -Treatment failure is higher in prior use of LAM or LAM-resistance so *AVOID in prior LAM use or LAM resistance*

Cigarette smoking and IBD conundrum

Smoking increases risk of developing *crohns NOT UC* Smoking *cessation increases risk of UC flare* while smoking cessation decreases disease severity of CD Increased exposure to smoking increases risk of developing CD The *risk of UC is highest in the first 2-5 years after smoking cessation* but remains elevated for > 20 years.

Sofosbuvir

Sovaldi

Consequences of long term (chronic pain)

Spinal sensitization - increased response to noxious stimuli

Goals of lung cancer treatment by stage

Stage I-III: Goal usually cure Stage IV (metastatic) - goal is usually palliative (symptom control)

Basics of what stage to do adjuvant chemotherapy for lung cancer

Stage IA: No chemo = worsened survival Stage IB: Controversial, usually only chemo if high risk features. ASCO and NCCN conflict. Stage II and IIIA: Adjuvant chemo with Cisplatin based regimen (ASCO and NCCN agree). LACE metaanalysis trial. Stage IIB and Higher: Chemo usually with other targeted therapy and radiation. Usually can't do surgery.

Benefits of thiopurines (AZA and 6-MP) in treatment of IBD

Steroid sparing *Fewer admission to hospital* Fewer operations Used in patients who *Failed standard treatment or are corticosteroid dependent* MAINTENANCE ONLY Must combine with other acute therapies due to delayed onset of *at LEAST 3 months*

SRMB Prevention Guideline

Stress Ulcer Prophylaxis should only be given to: 1. Patients with *respiratory failure or coagulopathy* (MAJOR risk factors) 2. Patients with *at least two other risk factors* listed (non-major risk) Enteral nutrition may lower risk of acute GI bleed due to stress ulcer, however anti-secretory agents are first line for prophylaxis -Antisecratory agents are used to maintain *intragastric pH > 4*

Actemra dosage forms

SubQ IV

Simponi (golimumab) dosage forms

SubQ = Simponi IV infusion = Simponi Aria but *RA only*

Kevzara (sarilumab) dosage forms

SubQ only

Which antiemetic should NOT be used for breathrough treatment of N/V?

Substance P/NK1 antagonists

2018 PADIS guidelines for sedation therapy

Suggest *propofol or dexmedetomidine* over benzodiazepines in critically ill *mechanically ventilated* adults

What is the safest DMARD in pregnancy

Sulfsalazine (Cat B) Hydroxychloroquine is a close second

What do you do if patient has severe GI symptoms and is getting worse after a few weeks of a ganciclovir IV regimen?

Suspect CMV resistance 1. Increase (basically double) ganciclovir dose 2. Start cidofovir or foscarnet

The Quick SOFA (qSOFA)

Suspected infection PLUS 2 of: 1. Resp rate *>/= 22/min* 2. Altered mental status 3. SBP </= 100 mm Hg

ADV-resistant first line option

Switch to *TDF first line* - studies show effectiveness

Recommended HBV antiviral in renal disease

TAF - no dose adjustment if CrCl is > 15 mL/min If in HD patient, give after HD All others need dose adjustment if CrCl < 50 mL/min

Most common and recommended regimen for post-transplant maintenance

Tacrolimus Mycophenolate Prednisone

Dose reduction of CIs with voriconazole

Tacrolimus = dose reduce to *1/3 original* Cyclosporine = dose reduction to

Which HBV antiviral should be avoided in Child Pugh class B or C hepatic impairment?

Tenofovir alafenamide

Which HBV antiviral should be taken with food?

Tenofovir disproxil fumarate (Viread or TDF) and Tenofovir alafenamide

CDK4/6 Inhibitors

The "clibs" 1. Palbociclib (Ibrance) 2. Ribociclib (Kisqali) 3. Abemaciclib (Verzenio) CDK4/6 lies upstream of VEGF, NF-kB, DNA repair processes, E2F (tanscription factor) for cell division, etc

The new ACCP/SCCM Sepsis definitions got rid of what?

The *SIRS Criteria* >/= 2 of: -Temp > 38C or <36 C -HR > 90 bpm -Respirations > 20/min or arterial O2 < 32 mm Hg -WBC count > 12,000 or < 4,000 or > 10% immature neutrophils

Durvalumab mechanism of action

The other PDL-1 LIGAND binding MAb (besides atezolizumab) Blocking PDL-1 binding to CD80/86 (this is a normal immune checkpoint) results in increased T-cell activation vs the tumor

H2RAs and PUD re-bleeding

They are INEFFECTIVE because they do not achieve intragastric pH of > 6 + there is risk of *tachyphylaxis* PPIs decrease incidence of rebleed and need for surgery

anti-HBc

Total Hepatitis B *core* abtibody (+) = previous or current infection -Present at *onset of sx* in acute HBV infection -Stays *present for life*

TMPT toxicities with 6-MP

Toxicities attributed to metabolites 6-TG and 6-MMP (by TPMT) 6-TG = bone marrow suppression (IMPDH makes) 6-MMP leads to increased hepatotoxicity (if low TPMT activity will NOT make and force more to 6-TG) DO NOT USE if low to absent or homo recessive TPMT Dose reducce to 1/2 normal for intermediate activity or heterozygotes Normal dose for normal to high activity TPMT

Hydrocortisone, Vitamin C, and thiamine for treating severe sepsis and septic shock

Trials was small (47 patients) and nonreproducible but *mortality 8.5% in treatment vs 40.4% in control group*

Severity scoring tool for UC

Truelove and Witts Severity Index Looks at things like Hgb, *blood in stool*, number of stools, pulse, etc to determine mild, severe, or fulminant disease

Rituximab biosimilar on market

Truxima NOT approved for RA - only onc

T-staging for colon cancer

Tx - cannot be assessed T0 - no evidence Tis - carcinoma in situ (intraepithelial or invasion of laminal propria) T1 - tumor invades *submucosa* T2 - tumor invades muscularis pripria T3 - tumor invades through *muscularis propria into subserosa* T4 - tumor invades other organ or structures and/or *perforates visceral peritoneum*

Valganciclovir prophy dose and duration in moderate or low risk patients

UNKNOWN dose and duration -Many use lower 450 mg dose as alternative X 3-6 months, can use 900 mg but potentially more toxicity

Entyvio (vedolizumab) indications in IBD

Unlike natalizumab is indicated for *BOTH CD and UC* CD - induction and maintenance of response, remission, and corticosteroid free remission in patients *failing anti-TNF agents* or were corticosteroid dependent UC - induction and maint of respone, remission, and corticosteroid free remission in pts that failed anti-TNF agents or were corticosteroid dependent

AZA and 6-MP dose adjustments

Use interchangable Make sure to allow *2-4 weeks to reach SS* before any dose adjustments are made Lots of DDIs you may need to dose adjust for - Aminosalycilates (inhibit TPMT), XO inhibitors (allopurinol and febuxostate avoid , allo can dose reduce), immunosuppressants, warfarin, *furosemide* (inhibits TPMT), and *ACE inhibitors*

How long should you wait to get a trough level after changing the dose?

Usually *3-5 days* Half life is longer so have to wait until closer to steady state

Steroid dosing in rejection

Usually high doses in pulses for a short period of time Usually 250-1000 mg methylpred X 3 doses OR high dose oral prednisone taper

Methotrexate dosing in RA

Usually low dose < 20 mg Most importantly *WEEKLY*

ACEi DDI with cyclosporine or tacrolimus

Vasodilates the efferent arteriole leading to *reduced GFR* if used with CsA and TAC Remember, TAC and CsA vasoconstrict and can cause pre-renal AKI

NS5A Inhibitors for HepC

Velpatasvir (VEL) Elbasvir (EBR) Pibrentasvir (in Mavyret)

HepA Survival

Very hardy - survives in highly acidic GIT and outside body for months Boil/cook at least 1 minute or BLEACH

Chemotherapy options for SCLC

Very similar to NSCLC, just NO pemetrexed -Cisplatin or carboplatin + etoposide -Cisplatin or carboplatin + irinotecan *Progressed...possibly add* -Paclitaxel and docetaxel -Irinotecan, topotecan if not tried already -Temozolomide -Gemcitabine -CAV = cyclophosphamide, doxorubicin, and vincristine

CYP interactions with cyclosporine and tacro

Voriconazole > posaconazole > itraconazole > fluconazole

Sofosbuvir/Velpatasvir/Voxilaprevir

Vosevi

Goal with nitrogen in TPNs

Want *Nitrogen intake > output* - goal is 4-6 g/day *positive nitrogen balance* -Important for growth and other anabolic processing (e.g. wound healing) -It is very unusual to obtain a positive nitrogen balance in critically ill patients -*Negative N balance and malnutrition have shown to increase morbidity and mortality*

Day 1 Prophylaxis for HIGH emetogenic risk chemo

Want to prevent *acute emesis* 1. NK1 antagonists PLUS 5-HT3 antagonist + dexamethasone 2. NK1/5-HT3 antagonist PLUS dexamethasone 3. Olanzapine + 5-HT3 antagonist + dexamethasone

How does renal injury in RA usually occur?

We kill their kidneys with meds

Hydroxychloroquine onset time

Weeks to *months* for full effect

Plaquenil onset

Weeks to *months* for full effect - longer than MTX and others

When do you switch a patient from PN to EN? (starred)

When *GI function returns*

Low emetogenic chemo

Without prophy *10-30%* of patients will have n/v

Moderately emetogenic chemo

Without prophy *30-90%* of patients will have n/v

Highly emetogenic chemo

Without prophy *> 90%* of patients will have n/v

Dronabinol for antiemesis

Works in the *cerebral cortex* and inhibits pathways to the vomiting center *Adverse effects* -Euphoria -Dry mouth -*Sedation* -Ortho hypotension -Dizziness -Dysphoria -*Increased appetite*

Grazoprevir/Elbasvir

Zepatier

HCV drug that can increase AST

Zepatier

HCV drugs to avoid in liver disease (Child Pugh B and C) and decompensated cirrhosis

Zepatier (grazoprevir/elbasvir) Vorsevi (SOF/velpatasvir/voxilaprevir) Mavyret (glecaprevir/pibrentasvir)

HepC meds with Hepatic concen

Zepatier (grazoprevir/elbasvir) Vosevi (sofosbuvir/voxilaprevir) Mavyret (Glecaprevir/pibrentasvir) *Note: All meds with a NS3/4A inhibitor*

Obese BMI

over 30 If > 40 morbidly obese If >35 + obesity related health conditions like HTN or DM then also morbid obesity